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Latest Research on Diabetes
     
Diabetes Technol Ther. 2008 Apr;10(2):121-7.
The long-term efficacy of insulin glargine plus oral antidiabetic agents in a 32-month observational study of everyday clinical practice.
Schreiber SA, Ferlinz K, Haak T.
Diabeteszentrum Schreiber, Quickborn, Germany.

ABSTRACT Background: Maintaining target glycosylated hemoglobin (HbA(1c)) (<7%) in patients with type 2 diabetes mellitus (T2DM) reduces the risk of late diabetes-associated complications. Previously reported results of a 9-month, uncontrolled, observational study (n = 12,216) showed that the addition of insulin glargine, a basal insulin analog, to existing oral antidiabetic drug (OAD) therapy was associated with reductions in HbA(1c) to target levels. This analysis investigated the effects of long-term, once-daily insulin glargine plus OAD therapy on glycemic control in patients with T2DM in a 32-month extension of the original observational study. Methods: After 9 months of observation, an extension of up to 32 months was offered to the participating physicians. The 32-month data were available for 1,915 patients. Results: At baseline, mean +/- standard deviation age was 63.5 +/- 11.3 years, HbA(1c) was 8.6 +/- 1.5%, fasting blood glucose (FBG) level was 200.7 +/- 57.8 mg/dL (11.1 +/- 3.2 mmol/L), and body mass index (BMI) was 29.0 +/- 4.8 kg/m(2). Reductions in HbA(1c) (-1.7%) and FBG (-71.4 mg/dL [-4.0 mmol/L]) were observed after 9 months of treatment with insulin glargine plus OADs and were maintained at 32 months (HbA(1c), -1.6%; FBG, -71.8 mg/dL [-4.0 mmol/L]). These improvements were broadly consistent across all BMI categories. Conclusions: These data suggest that in daily practice the introduction of insulin glargine with continued OAD therapy facilitates both attainment and maintenance of target HbA(1c) levels, irrespective of BMI in patients with T2DM.

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Acta Diabetol. 2008 Mar;45(1):61-6. Epub 2008 Jan 29.
Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.
Lapolla A, Dalfrà MG, Spezia R, Anichini R, Bonomo M, Bruttomesso D, Di Cianni G, Franzetti I, Galluzzo A, Mello G, Menato G, Napoli A, Noacco G, Parretti E, Santini C, Scaldaferri E, Scaldaferri L, Songini M, Tonutti L, Torlone E, Gentilella R, Rossi A, Valle D.
Dipartimento Scienze Mediche e Chirurgiche, Cattedra di Malattie del Metabolismo, Università di Padova, Via Giustiniani, 2, 35100, Padua, Italy, annunziata.lapolla@unipd.it.

Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.

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Am J Med. 2008 Feb;121(2):149-157.e2.
Meta-analysis: metformin treatment in persons at risk for diabetes mellitus.
Salpeter SR, Buckley NS, Kahn JA, Salpeter EE.
Santa Clara Valley Medical Center, San Jose, CA 95128, USA. salpeter@stanford.edu

PURPOSE: We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes. METHODS: We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes. RESULTS: Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (-5.3%, 95% confidence interval [CI], -6.7--4.0), fasting glucose (-4.5%, CI, -6.0--3.0), fasting insulin (-14.4%, CI, -19.9--8.9), calculated insulin resistance (-22.6%, CI, -27.3--18.0), triglycerides (-5.3%, CI, -10.5--0.03), and low-density lipoprotein cholesterol (-5.6%, CI, -8.3--3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years. CONCLUSION: Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials.

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Clin Res Cardiol. 2008 Feb 4 [Epub ahead of print]
The Euro Heart Survey - Germany: diabetes mellitus remains unrecognized in patients with coronary artery disease.
Drechsler K, Fikenzer S, Sechtem U, Blank E, Breithardt G, Zeymer U, Niebauer J.
Klinik für Kardiologie, Herzzentrum Leipzig, Leipzig, Germany.

AIM: Diabetes mellitus is associated with a poor prognosis due to a high rate of coronary artery disease. It was the aim of this survey to assess the prevalence of an impaired glucose tolerance and manifest diabetes mellitus in patients with coronary artery disease (CAD). METHODS: We analyzed data of all German centers participating in the Euro Heart Survey on diabetes and the heart, an European-wide multicenter prospective observational study. Participating centers were asked to recruit patients >18 years with a diagnosis of CAD. RESULTS: In Germany, 261 patients with a diagnosis of CAD were enrolled in five participating centers. Patients were divided into an acutely (22,4%; n = 57) or electively admitted (77,6%; n = 198) group. There were 34% (n = 89) of patients with already known diabetes. In 36% (n = 22 of 56) of the patients without previously known diabetes, an oral glucose tolerance test (OGTT) was performed (3%, n = 5 in the acute and 33%, n = 51 in the elective group). As a result, 39% (n = 22 of 56) of these patients had an impaired glucose tolerance (acute group: 0%, n = 0 of 5; elective group: 43%, n = 22 of 51) and in 13% (n = 7 of 56) diabetes mellitus was diagnosed (acute group: 40%, n = 2 of 5; elective group: 10%, n = 5 of 51). Furthermore, on admission 86% of women and 94% of men reported to exercise less than three times per week and thus less than recommended in current guidelines. CONCLUSION: More than one third of the patients with CAD who underwent an OGTT had an impaired glucose tolerance. Implementation of this simple, effective and inexpensive test into clinical routine of patients with CAD would help diagnose diabetes mellitus and thus grant these high risk patients access to an optimal medical, interventional and surgical therapy. Furthermore, patients ought to be encouraged to include exercise training into their daily routine.

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Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006061.
Whole grain foods for the prevention of type 2 diabetes mellitus.
Priebe M, van Binsbergen J, de Vos R, Vonk R.

BACKGROUND: Diet as one aspect of lifestyle is thought to be one of the modifiable risk factors for the development of type 2 diabetes mellitus (T2DM). Information is needed as to which components of the diet could be protective for this disease. OBJECTIVES: To asses the effects of whole-grain foods for the prevention of T2DM. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and AMED. SELECTION CRITERIA: We selected cohort studies with a minimum duration of five years that assessed the association between intake of whole-grain foods or cereal fibre and incidence of T2DM. Randomised controlled trials lasting at least six weeks were selected that assessed the effect of a diet rich in whole-grain foods compared to a diet rich in refined grain foods on T2DM and its major risk factors. DATA COLLECTION AND ANALYSIS: Two authors independently selected the studies, assessed study quality and extracted data. Data of studies were not pooled because of methodological diversity. MAIN RESULTS: One randomised controlled trial and eleven prospective cohort studies were identified. The randomised controlled trial, which was of low methodological quality, reported the change in insulin sensitivity in 12 obese hyperinsulinemic participants after six-week long interventions. Intake of whole grain foods resulted in a slight improvement of insulin sensitivity and no adverse effects. Patient satisfaction, health related quality of life, total mortality and morbidity was not reported.Four of the eleven cohort studies measured cereal fibre intake, three studies whole grain intake and two studies both. Two studies measured the change in whole grain food intake and one of them also change in cereal fibre intake. The incidence of T2DM was assessed in nine studies and changes in weight gain in two studies. The prospective studies consistently showed a reduced risk for high intake of whole grain foods (27% to 30%) or cereal fibre (28% to 37%) on the development
of T2DM. AUTHORS' CONCLUSIONS: The evidence from only prospective cohort trials is considered to be too weak to be able to draw a definite conclusion about the preventive effect of whole grain foods on the development of T2DM. Properly designed long-term randomised controlled trials are needed. To facilitate this, further mechanistic research should focus on finding a set of relevant intermediate endpoints for T2DM and on identifying genetic subgroups of the population at risk that are most susceptible to dietary intervention.

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Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003205.
Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus.
Hartweg J, Perera R, Montori V, Dinneen S, Neil H, Farmer A.

BACKGROUND: People with type 2 diabetes mellitus are at increased risk from cardiovascular disease. Dietary omega-3 polyunsaturated fatty acids (PUFAs) are known to reduce triglyceride levels, but their impact on cholesterol levels, glycemic control and vascular outcomes are not well known. OBJECTIVES: To determine the effects of omega-3 PUFA supplementation on cardiovascular outcomes, cholesterol levels and glycemic control in people with type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, bibliographies of relevant papers and contacted experts for identifying additional trials. SELECTION CRITERIA: All randomised controlled trials were included where omega-3 PUFA supplementation or dietary intake was randomly allocated and unconfounded in people with type 2 diabetes. Authors of large trials were contacted for missing information. DATA COLLECTION AND ANALYSIS: Trials were assessed for inclusion. Authors were contacted for missing information. Data was extracted and quality assessed independently in duplicate. Fixed-effect meta-analysis was carried out. MAIN RESULTS: Twenty three randomised controlled trials (1075 participants) were included with a mean treatment duration of 8.9 weeks. The mean dose of omega-3 PUFA used in the trials was 3.5 g/d. No trials with vascular events or mortality endpoints were identified. Among those taking omega-3 PUFA triglyceride levels were significantly lowered by 0.45 mmol/L (95% confidence interval (CI) -0.58 to -0.32, P < 0.00001) and VLDL cholesterol lowered by -0.07 mmol/L (95% CI -0.13 to 0.00, P = 0.04). LDL cholesterol levels were raised by 0.11 mmol/L (95% CI 0.00 to 0.22, P = 0.05). No significant change in or total or HDL cholesterol, HbA1c, fasting glucose, fasting insulin or body weight was observed. The increase in VLDL remained significant only in trials of longer duration and in hypertriglyceridemic patients. The elevation in LDL cholesterol was non-significant in subgroup analyses. No adverse effects of the intervention were reported. AUTHORS' CONCLUSIONS: Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed.

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Adv Cardiol. 2008;45:82-106.
Hypertension and diabetes.
Grossman E, Messerli FH.
Department of Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Both essential hypertension and diabetes mellitus affect the same major target organs. The common denominator of hypertensive/diabetic target organ-disease is the vascular tree. Left ventricular hypertrophy and coronary artery disease are much more common in diabetic hypertensive patients than in patients suffering from hypertension or diabetes alone. The combined presence of hypertension and diabetes concomitantly accelerates the decrease in renal function, the development of diabetic retinopathy and the development of cerebral diseases. Lowering blood pressure to less than 130/80mm Hg is the primary goal in the management of the hypertensive diabetic patients. Beta-blockers have been reported to adversely affect the overall risk factor profile in the diabetic patient. In contrast, calcium antagonists, angiotensinconverting enzyme inhibitors and angiotensin receptor blockers have been reported to be either neutral or beneficial with regard to the overall metabolic risk factor profile. Combination therapy is usually required to achieve blood pressure goal in diabetic patients. The addition of aldosterone antagonists may be beneficial in patients with resistant hypertension and low levels of serum potassium. Aggressive control of blood pressure, cholesterol and glucose levels should be attempted to reduce the cardiovascular risk of diabetic hypertensive patients.

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Ned Tijdschr Geneeskd. 2007 Dec 22;151(51):2833-7.
[Cinnamon: not suitable for the treatment of diabetes mellitus]
[Article in Dutch]
Kleefstra N, Logtenberg SJ, Houweling ST, Verhoeven S, Bilo HJ.
Isala klinieken, Diabetes Kenniscentrum, Zwolle. kleefstra@langerhans.com

OBJECTIVE: To identify published studies evaluating the effects of cinnamon on glycaemic control. DESIGN: Literature search. METHOD: The Medline database was searched using all possible combinations of the words and medical subject headings (MeSH) 'cinnamon', 'diabetes mellitus', 'HbA1C' and 'glucose'. All human or animal studies in which cinnamon was administered as intervention were included. RESULTS: Several animal studies and 5 randomized placebo-controlled trials in humans were found. Most of the animal studies described beneficial effects of cinnamon on glycaemic control. One placebo-controlled trial in patients with type 2 diabetes found that cinnamon intake was associated with favourable effects on fasting plasma glucose. None of the studies reported an improvement in HbA1C. A study in patients with type 1 diabetes found that cinnamon had no effect. CONCLUSION: Based on the currently available evidence, cinnamon should not be recommended for the improvement ofglycaemic control.

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Evid Based Complement Alternat Med. 2007 Dec;4(4):469-86.
The influence of yoga-based programs on risk profiles in adults with type 2 diabetes mellitus: a systematic review.
Innes KE, Vincent HK.
Center for the Study of Complementary and Alternative Therapies and Department of Physical Medicine and Rehabilitation, University of Virginia Health Systems, Charlottesville, VA, USA.

There is growing evidence that yoga may offer a safe and cost-effective intervention for Type 2 Diabetes mellitus (DM 2). However, systematic reviews are lacking. This article critically reviews the published literature regarding the effects of yoga-based programs on physiologic and anthropometric risk profiles and related clinical outcomes in adults with DM 2. We performed a comprehensive literature search using four computerized English and Indian scientific databases. The search was restricted to original studies (1970-2006) that evaluated the metabolic and clinical effects of yoga in adults with DM 2. Studies targeting clinical populations with cardiovascular disorders that included adults with comorbid DM were also evaluated. Data were extracted regarding study design, setting, target population, intervention, comparison group or condition, outcome assessment, data analysis and presentation, follow-up, and key results, and the quality of each study was evaluated according to specific predetermined criteria. We identified 25 eligible studies, including 15 uncontrolled trials, 6 non-randomized controlled trials and 4 randomized controlled trials (RCTs). Overall, these studies suggest beneficial changes in several risk indices, including glucose tolerance and insulin sensitivity, lipid profiles, anthropometric characteristics, blood pressure, oxidative stress, coagulation profiles, sympathetic activation and pulmonary function, as well as improvement in specific clinical outcomes. Yoga may improve risk profiles in adults with DM 2, and may have promise for the prevention and management of cardiovascular complications in this population. However, the limitations characterizing most studies preclude drawing firm conclusions. Additional high-quality RCTs are needed to confirm and further elucidate the effects of standardized yoga programs in populations with DM 2.

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Med Sci Monit. 2007 Dec 1;13(12):CR533-537.
Insulin treatment reduces pre-prandial plasma ghrelin concentrations in children with type 1 diabetes.
Ashraf A, Mick G, Meleth S, Wang X, McCormick K.
Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, The Children’s Hospital, University of Alabama at Birmingham, Birmingham, AL, U.S.A.

Background: Ghrelin is well recognized as a key factor in regulating appetite and energy homeostasis. The aim of the present study is to characterize the plasma ghrelin concentrations in children with type 1 diabetes at the time of diagnosis and to determine the effect of metabolic control after insulin therapy on circulating ghrelin levels. Also, the relationship between the simultaneous blood glucose concentrations and fasting plasma ghrelin concentrations was explored. Material/Methods: This prospective study assessed the changes in pre-prandial plasma ghrelin levels after treatment of type 1 diabetes with insulin. Results: The study comprised 19 children with new onset diabetes mellitus. Mean plasma ghrelin levels declined by 29% in diabetic children post insulin treatment (p=0.007). There was a significant correlation between plasma ghrelin and body mass index (BMI) in children with type 1 diabetes at diagnosis (r=-0.54), but not at follow up. The difference in ghrelin at diagnosis and at 3 month follow up demonstrated an inverse relationship to difference in plasma glucose (r=-0.48). Conclusions: Plasma ghrelin concentrations could be suppressed in untreated type 1 diabetic children by improved glycemic control following insulin replacement.

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Clin Ther. 2007;29 Spec No:1306-15.
Comparisons of rosiglitazone versus pioglitazone monotherapy introduction and associated health care utilization in medicaid-enrolled patients with type 2 diabetes mellitus.
Balkrishnan R, Arondekar BV, Camacho FT, Shenolikar RA, Horblyuk R, Anderson RT.
Department of Pharmacy Practice and Administration, The Ohio State University, College of Pharmacy and School of Public Health, Columbus, Ohio 43210, USA. balkrishnan.1@osu.edu

BACKGROUND: Outcomes in patients with type 2 diabetes mellitus (DM) can differ based on the antidiabetic medication that is used. Thiazolidinediones (TZDs) are a newer class of agents used for the treatment of type 2 DM. No previous study has compared health care utilization associated with the 2 TZDs on the market. OBJECTIVE: The objective of this study was to compare health care utilization and costs associated with initiation of treatment with either rosiglitazone or pioglitazone by Medicaid-enrolled patients with type 2 DM. METHODS: This was a retrospective data analysis comparing cohorts of patients with type 2 DM starting a new antidiabetic medication in terms of hospitalizations, emergency department visits, outpatient physician visits, and health care costs reimbursed by the North Carolina Medicaid program. The perspective adopted in this analysis was that of the third-party payer (ie, the North Carolina Medicaid program). Patients starting rosiglitazone between July 1, 2001, and June 30, 2002, were compared with patients starting pioglitazone during the same period. The patients were followed up for 30 months to examine the difference in health care utilization over time. Multivariate regression techniques were employed for comparisons between the 2 different antidiabetic therapies. RESULTS: A total of 1705 patients with type 2 DM were identified and included in the final cohort. There were 660 patients (mean [SD] age, 49.0 [10.2] years) in the rosiglitazone arm and 1045 patients (mean [SD] age, 49.1 [10.5] years) in the pioglitazone arm. Multivariate analysis showed that the rosiglitazone monotherapy group was associated with a 12.2% decrease in the mean number of hospitalizations, a 10.4% decrease in the mean number of emergency department visits, and a 7.3% decrease in total health care costs compared with the pioglitazone monotherapy group (all, P < 0.05). This study only looked at patients who used the same drug for the entire follow-up period. It did not account for drug switching or addition of a new drug to an existing therapy. CONCLUSIONS: Introduction of rosiglitazone was associated with a decreased number of hospitalizations, emergency department visits, and total health care costs compared with pioglitazone. The utilization of oral antidiabetic agents, with documented clinical and economic benefits, should continue to be advocated to reduce avoidable medical care utilization and to improve patient outcomes in this population.

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Clin Ther. 2007;29 Spec No:1271-83.
Developing a pulmonary insulin delivery system for patients with diabetes.
Dailey G.
Division of Diabetes and Endocrinology, Scripps Clinic, La Jolla, California 92037, USA. dailey.george@scrippshealth.org

BACKGROUND: Many patients with type 1 or type 2 diabetes mellitus (DM) do not achieve recommended glycemic goals. Insulin therapy is often delayed, despite its effectiveness in maintaining glycemic control, for reasons such as fear of needles or dislike of the complexity of injections. Inhaled dry powder insulin (IDPI) is approved for preprandial use in both the United States and Europe. METHODS: Relevant English-language publications were identified through a search of the PubMed database (1980-2007). Search terms included diabetes, in combination with subcutaneous and/or inhaled insulin. A similar search of abstracts from the 2006 American Diabetes Association 66th Annual Scientific Sessions was also performed. RESULTS: Eight clinical studies to date have reported that IDPI consistently improved glycemic control, whether used in combination with longer-acting SC insulin regimens in patients with type 1 or type 2 DM or to supplement or replace oral agent therapy in patients with type 2 DM. Evidence to date suggests that IDPI is associated with an acceptable tolerability profile, with a risk of hypoglycemia similar to that of SC insulin (risk ratios in 2 studies were 0.94 and 0.96, in favor of IDPI). Moreover, no clinically significant changes in pulmonary function have been noted. Patients treated with IDPI in clinical studies reported significantly greater improvements in overall satisfaction with treatment compared with SC insulin (P < 0.01) or oral agent therapy (P = 0.02). CONCLUSION: IDPI is effective and well tolerated for the treatment of diabetes and may be an option for patients to achieve glycemic control.

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Clin Ther. 2007;29 Spec No:1236-53.
Advancing therapy in type 2 diabetes mellitus with early, comprehensive progression from oral agents to insulin therapy.
Vinik A.
Strelitz Diabetes Research Institute, Eastern Virginia Medical School, Norfolk, Virginia, USA. Vinikai@evms.edu

BACKGROUND: Early and intensive glycemic control is necessary to prevent or minimize the development of microvascular and macrovascular complications in individuals with type 2 diabetes mellitus. However, many patients are unable to attain glycemic control, partly due to protracted treatment with oral antidiabetic drugs (OADs) despite inadequate control and barriers to initiating insulin therapy. Patients at different stages of disease may benefit from the early introduction of intensive glycemic control. OBJECTIVE: This article discusses some of the potential barriers to achieving and maintaining optimal glycemic levels in patients whose blood glucose is sub-optimally controlled with OADs and reviews the benefits of early introduction of intensive glycemic control in patients at various stages of disease, with an emphasis on insulin therapy. METHODS: Relevant English-language articles published from 1996 to 2006 were identified through searches of the National Center for Biotechnology PubMed database. Search terms included insulin, insulin therapy, type 2 diabetes, insulin analogs, early insulinization, and diabetes prevention, among others. Studies were assessed regarding designs, primary and secondary efficacy parameters, glycosylated hemoglobin (HbA1c), fasting plasma glucose, incidence of hypoglycemia, and other safety assessments. Inclusion criteria were multicenter, randomized, open-label, parallel-group trials, as well as retrospective observational studies, conducted in Europe or the United States. Additional analyses and guideline-based recommendations are included. RESULTS: The landmark results of the United Kingdom Prospective Diabetes Study, which found that an intensive strategy in 3867 newly diagnosed patients with type 2 diabetes was associated with stricter glycemic control than was conventional care (HbA1c over 10 years, 7.0% vs 7.9%; P < 0.001), as well as a 25% reduction in the risk for microvascular complications (P = 0.01). Early initiation of insulin therapy concomitantly with OADs appeared well tolerated in the populations studied, was effective in recently diagnosed patients, and may also confer anti-inflammatory and antiatherogenic effects. Characteristics associated with newer formulations of insulin (eg, basal insulin analogues as well as rapid-acting insulin analogues, the insulin pump, or inhaled insulin) may help overcome barriers associated with initiating insulin therapy. CONCLUSIONS: Based on the literature, early and persistent intensification of antidiabetic therapy is an approach that most likely will achieve optimal glycemic control in patients with type 2 diabetes and help prevent associated complications. Greater clinical experience with newer therapeutic approaches, including incretin mimetics and dipeptidyl peptidase-IV inhibitors, will provide insight into their place in the spectrum of diabetes treatments.

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Am J Kidney Dis. 2007 Dec;50(6):946-51.
A randomized trial of a 6-week course of celecoxib on proteinuria in diabetic kidney disease.
Sinsakul M, Sika M, Rodby R, Middleton J, Shyr Y, Chen H, Han E, Lehrich R, Clyne S, Schulman G, Harris R, Lewis J.
Rush University Medical Center, Chicago, IL 60607, USA. marvin_v_sinsakul@rush.edu

BACKGROUND: Preclinical data suggest that cyclooxygenase 2 inhibitors decrease proteinuria and preserve glomerular structure in animal models of diabetic nephropathy. The objective of this study is to compare the efficacy and safety of celecoxib with placebo for decreasing proteinuria in patients with diabetic nephropathy. STUDY DESIGN: Placebo-controlled double-blinded crossover design. SETTING & PARTICIPANTS: 24 patients with type 1 or 2 diabetes mellitus, proteinuria with protein of 500 mg/d or greater, and serum creatinine level of 3.0 mg/dL or less. INTERVENTION: Patients were randomly assigned to: (1) 6 weeks of celecoxib followed by a 3-week washout period, followed by 6 weeks of placebo followed by another 3-week washout; or (2) 6 weeks of placebo followed by a 3-week washout, followed by 6 weeks of celecoxib followed by another 3-week washout period. All patients were administered quinapril, 20 to 40 mg/d, or irbesartan, 150 to 300 mg/d. All patients were administered aspirin, 81 mg/d. OUTCOMES & MEASUREMENTS: Proteinuria was assessed by means of protein-creatinine ratio. Data were analyzed using the mixed-effect statistical model. RESULTS: There was no significant difference in urinary proteinuria after 6 weeks of treatment with placebo or celecoxib (proteinuria ratio, celecoxib versus placebo, 1.041; 95% confidence interval, 0.846 to 1.282). Celecoxib had no significant effect on potassium or estimated glomerular filtration rate. Frequencies of adverse events were similar between the placebo and celecoxib treatments. LIMITATIONS: This pilot study was not designed to evaluate the safety or long-term clinical effects of celecoxib. CONCLUSIONS: Celecoxib, 200 mg/d, for 6 weeks did not alter proteinuria. Few adverse events were noted in this high-risk population

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Pediatr Diabetes. 2007 Dec;8(6):377-83.
Continuous subcutaneous insulin infusion benefits quality of life in preschool-age children with type 1 diabetes mellitus.
Opipari-Arrigan L, Fredericks EM, Burkhart N, Dale L, Hodge M, Foster C.
Division of Child Behavioral Health, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.

Objective: To compare medical, nutritional, and psychosocial outcomes of continuous subcutaneous insulin infusion (CSII) therapy and multiple daily insulin injections (MDI) in preschoolers with type 1 diabetes mellitus (T1DM) in a randomized controlled trial. Study design: Sixteen children (mean age 4.4 +/- 0.7 yr, range 3.1-5.3 yr) with T1DM were randomly assigned to CSII or MDI. Hemoglobin A1c (HbA1c) was measured monthly for 6 months. Glucose variability was measured at baseline and at 6 months using continuous blood glucose sensing. Quality of life, adverse events, and nutrition information were assessed. Results: Parents of the CSII group reported a significant decrease in diabetes-related worry, while parents of the MDI group reported an increased frequency of stress associated with their child's medical care. Mean HbA1c levels from baseline (CSII 8.3 +/- 1.4%, MDI 8.0 +/- 0.8%) to 6 months (CSII 8.4 +/- 0.8%, MDI 8.2 +/- 0.4%) remained stable, and group differences were not significant. There were no significant group differences in duration of hypo- or hyperglycemic events or frequency of adverse events. Conclusion(s): For young children with T1DM, CSII therapy is comparable to MDI therapy with regard to glucose control but is associated with higher treatment satisfaction and improved quality of life.

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Expert Opin Pharmacother. 2007 Dec;8(18):3147-58.
Prevention of Type 2 diabetes: fact or fiction?
Chiasson JL.
Université de Montréal, Research Group on Diabetes and Metabolic Regulation Research Centre, CHUM - Hôtel-Dieu, Department of Medicine, Montreal, Canada. jean.louis.chiasson@umontreal.ca

The growing prevalence of Type 2 diabetes with its high morbidity and excess mortality is imposing a heavy burden on healthcare systems. Because of the magnitude of the problem, obviating diabetes has been a long-standing dream. In the last decade, a number of intervention strategies have been shown to be effective for the prevention of diabetes in high-risk populations with prediabetes. Seven studies have now confirmed that lifestyle modifications, including weight-reducing diets and exercise programs, are very effective in precluding or delaying Type 2 diabetes in high-risk populations with impaired glucose tolerance (IGT). Two major trials are the Diabetes Prevention Study (n = 522) from Finland and the Diabetes Prevention Program (n = 3234) from the US. Both studies have shown that intensive lifestyle intervention could reduce the progression of IGT to diabetes by 58%. Furthermore, four currently-available drugs have been established as being effective in preventing diabetes in subjects with prediabetes. The Diabetes Prevention Program revealed that metformin 850 mg b.i.d. reduced the risk of diabetes by 31%. The STOP-NIDDM (Study To Prevent Non-Insulin-Dependent Diabetes Mellitus) trial (n = 1429) showed that acarbose 100 mg t.i.d. with meals decreased the incidence of diabetes by 36% when the diagnosis was based on 2 oral glucose tolerance tests. The XENDOS (Xenical in the Prevention of Diabetes in Obese Subjects) study examined the use of orlistat, an antiobesity drug, as an adjunct to an intensive lifestyle modification program in obese non-diabetic subjects. Orlistat treatment resulted in a 37% decline in the development of diabetes. More recently, the DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication) study (n = 5269) demonstrated that rosiglitazone at 8 mg once/day in subjects with prediabetes (IGT and/or impaired fasting glucose) was effective in reducing the risk of diabetes by 60%. It can be concluded that Type 2 diabetes can be prevented or delayed through lifestyle modifications and/or pharmacologic interventions. This is a fact.

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Clin Ther. 2007 Sep;29(9):1900-14.
A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy and tolerability of combination therapy with rosiglitazone and sulfonylurea in African American and Hispanic American patients with type 2 diabetes inadequately controlled with sulfonylurea monotherapy.
Davidson JA, McMorn SO, Waterhouse BR, Cobitz AR.
Department of Medicine, University of Texas, Southwestern Medical School, Dallas, Texas 75248, USA. davidsonmd@sbcglobal.net

BACKGROUND: Type 2 diabetes mellitus is twice as prevalent in African Americans and Hispanic Americans as in non-Hispanic whites. However, the effectiveness and safety profile of rosiglitazone maleate used as combination therapy with sulfonylureas in the management of diabetes and its effect on cardiovascular disease (CVD) biomarkers/parameters have not been studied in these populations. OBJECTIVE: The purpose of this study was to determine the efficacy and tolerability of the addition of rosiglitazone to a regimen of glyburide once daily in African American and Hispanic American patients with type 2 diabetes previously inadequately controlled with sulfonylurea monotherapy. METHODS: This randomized, double-blind, placebo-controlled, parallel-group study was conducted at 38 centers in the United States. Eligible patients were aged < or =21 years, had type 2 diabetes, a fasting plasma glucose (FPG) level > or =140 mg/dL, and a glycosylated hemoglobin (HbA(1c)) value > or =7.5%, and had been treated with sulfonylurea monotherapy for at least 2 months before screening. Patients were assigned to receive treatment with glyburide 10 or 20 mg/d plus rosiglitazone 8 mg (GLY+RSG) or placebo (GLY+PBO) PO (tablets) QD for 24 weeks. The primary efficacy end point was the change from baseline in HbA(1c) after 24 weeks of treatment. Secondary end points included change in FPG; proportion of patients achieving HbA(1c) targets (<7.0% and <6.5%); and changes in biomarkers for CVD risk, including C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-I activity, fibrinogen, tissue plasminogen activator (tPA) antigen, von Willebrand factor (vWF), soluble vascular cell adhesion molecule (sVCAM), lipoprotein-associated phospholipase A 2 activity, and urinary albumin/creatinine ratio (UACR). Tolerability was assessed using physical examination, including vital-sign measurement, clinical laboratory tests, and adverse event (AE) reports collected at each study visit. RESULTS: A total of 245 patients (101 African American and 144 Hispanic American) were enrolled. Demographic characteristics were comparable between the GLY+RSG and GLY+PBO groups: mean (SD) age (52 [11.9] vs 53 [10.4] years), HbA(1c) (9.2% [1.3%] vs 9.4% [1.4%]), sex (men/women, 45.3%/54.7% vs 48.3%/51.7%), race (African American/Hispanic American, 43.6%/56.4% vs 37.9%/62.1%), and mean (SD) weight (86.3 [18.8] vs 88.3 [19.4] kg). In the overall study population, treatment with GLY+RSG was associated with a significantly greater mean (95% CI) reduction from baseline in HbA(1c) compared with GLY+PBO (between-group Delta, -1.4% [-1.7% to -1.1%]; P < 0.001). When assessed by ethnicity, HbA(1c) values were significantly reduced with GLY+RSG compared with GLY+PBO in African American patients (between-group Delta, -1.4%) and in Hispanic American patients (between-group Delta, -1.5%) (both, P < 0.001), as were FPG levels (between-group Deltas, -3.1 mmol/L [57 mg/dL] and -3.8 mmol/L [-69 mg/dL], respectively; both, P < 0.001). With GLY+RSG, 9151 (17.6%) African American patients and 17/66 (25.8%) Hispanic American patients achieved HbA(1c) <7%, compared with 2/44 (4.5%) and 1/72 (1.4%) patients, respectively, who achieved this goal with GLY+PBO. Homeostasis model assessment estimates of insulin sensitivity and beta-cell function were significantly improved with GLY+RSG compared with GIX+PBO (between-group Deltas, 29.3% and 78.4%, respectively; both, P < 0.001). With regard to CVD biomarkers, there were potentially deleterious changes compared with baseline in the GLY+PBO group for CRP (+29.4%; P = 0.042), PAI-1 activity (+27.0%; P = 0.006), fibrinogen (+15.7%; P = 0.007), and sVCAM (+7.0%; P = 0.035), whereas there were no significant increases in these factors in the GLY+RSG group. In the GLY+RSG group, there were significant improvements in tPA (-17.8%; P < 0.001), vWF (-11.3%; P = 0.019), and UACR (-17.2%; P = 0.028) over 24 weeks' treatment, whereas there were no significant changes in any of these factors in the GLY+PBO group. As a result, significant treatment effects were observed for CRP (-29.2%; P = 0.019), tPA (-18.4%; P < 0.001), vWF (-12.9%; P < 0.015), and UACR (-26.7%; P = 0.006) with GLY+RSG compared with GLY+PBO. The most frequently reported AEs with GLY+RSG were edema and weight increase (both 121121 [9.9%] patients) and with GLY+PBO were upper respiratory tract infection (18/124 [14.5%] patients). AEs were reported in 83/121 (68.6%) patients in the GLY+RSG group, of which 6/121 (5.0%) were assessed as severe, compared with 70/124 ( 56.5 % ) patients who received GLY+PBO, of which 31124 (2.4%) were assessed as severe. CONCLUSION: Add-on rosiglitazone administered for 24 weeks was effective and well tolerated in these African American and Hispanic American patients with type 2 diabetes previously inadequately controlled on sulfonylurea monotherapy.

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Med J Aust. 2007 Jun 18;186(12):622-4.
Management outcomes of patients with type 2 diabetes: targeting the 10-year absolute risk of coronary heart disease.
Yong TY, Phillipov G, Phillips PJ.
Endocrinology Unit, Queen Elizabeth II Hospital, Adelaide, SA, Australia. patrick.phillips@nwahs.sa.gov.au.

OBJECTIVE: To assess the management of patients with type 2 diabetes mellitus in the primary care setting, with respect to risk factors associated with coronary heart disease. DESIGN: Retrospective cross-sectional audit. SETTING: Specialised diabetes assessment clinic in a tertiary referral teaching hospital. PARTICIPANTS: 328 patients with type 2 diabetes mellitus (mean age, 58.3 years [95% CI, 57.5-59.1]) and no existing coronary heart disease (CHD) referred to the clinic by general practitioners during 2004-2005. MAIN OUTCOME MEASURES: Comparison of glycated haemoglobin (HbA(1c)), systolic blood pressure and total cholesterol levels and smoking frequency with current RACGP (Royal Australian College of General Practitioners) targets (< 7.0%; < 130/80 mmHg; < 4 mmol/L; and smoking cessation, respectively). Estimation of patients' 10-year absolute risk of CHD events using the United Kingdom Prospective Diabetes Study risk engine, and its relation to primary prevention of CHD. RESULTS: 42%, 61% and 43% of patients were receiving medication to treat hyperglycaemia, hypertension and hypercholesterolaemia, respectively; 46%, 29% and 15% of patients, respectively, had not achieved the recommended RACGP target values for HbA1c, blood pressure, and total cholesterol; and 22% of patients were current smokers. The mean 10-year absolute risk of CHD was 16.8% (95% CI, 15.7%-17.9%), and 48% of patients were classified as "high risk" (absolute risk, > 15%). Based on the 10-year absolute risk, there was no difference between high- and low-risk groups with respect to prescription of aspirin, statins or angiotensin-converting enzyme inhibitors. If all the recommended RACGP goals were achieved, the mean 10-year absolute risk would decrease to 12.6% (95% CI, 11.8%-13.4%). CONCLUSIONS: Recommended treatment targets are not being uniformly achieved. Medication for primary CHD prevention is not being preferentially directed at those patients at highest risk, based on the estimated 10-year absolute risk of CHD events. Our findings suggest new initiatives are required in the way target goals and primary CHD prevention measures are set for patients with type 2 diabetes mellitus.

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J Hypertens. 2007 Jun;25(6):1311-1317.
Diabetes in treated hypertension is common and carries a high cardiovascular risk: results from a 28-year follow-up.
Almgren T, Wilhelmsen L, Samuelsson O, Himmelmann A, Rosengren A, Andersson OK.
aDepartments of Internal Medicine bNephrology cClinical Pharmacology, Sahlgrenska University Hospital, Goteborg dDepartment of Medicine, Sahlgrenska University Hospital, Ostra, Goteborg eSection of Preventive Cardiology, the Cardiovascular Unit, Goteborg University, Goteborg, Sweden.

OBJECTIVE: The objective of this study was to analyse predictive factors for development of type 2 diabetes during life-long therapy for hypertension and the alleged additional cardiovascular risk this constitutes. METHODS: The study group (n = 754) comprised the hypertensive subgroup of a randomized population sample of 7500 men, aged 47-54 years, screened for cardiovascular risk factors and followed for 25-28 years. The patients were treated with thiazide diuretics and beta-adrenergic blocking drugs with the addition of hydralazin during the first decade. Calcium antagonists were substituted for hydralazin and, if needed, angiotensin-converting enzyme inhibitors were added when these drugs became available. RESULTS: A total of 148 (20.4%) treated hypertensive patients developed diabetes during 25 years, and in multivariate Cox regression analysis body mass index, serum triglycerides and treatment with beta-blockers were positively related with this complication. New-onset diabetes implied a significantly increased risk for stroke [hazard ratio (HR): 1.67; 95% confidence interval (95% CI): 1.1-2.6; P < 0.05], myocardial infarction (OR: 1.66; 95% CI: 1.1-2.5; P < 0.05) and mortality (OR: 1.42; 95% CI: 1.1-1.9; P < 0.05). The greatest risk for stroke was new-onset diabetes, followed by smoking (OR: 1.46; 95% CI: 1-2.2; P = 0.07) and the greatest risk for myocardial infarction was new-onset diabetes, followed by smoking (HR: 1.64; 95% CI: 1.1-2.4; P < 0.01). The greatest risk for mortality was smoking (HR: 1.73; 95% CI: 1.3-2.2; P < 0.005). Achieved systolic and diastolic blood pressure were not predictive of cardiovascular complications or death. The mean observation time from onset of diabetes mellitus to a first stroke was 9.1 years and to a first myocardial infarction 9.3 years. CONCLUSION: Diabetes in treated hypertensive patients is alarmingly common and carries a high risk for cardiovascular complications and mortality.

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Am J Health Syst Pharm. 2007 Jun 15;64(12):1265-1273.
Vildagliptin: A novel oral therapy for type 2 diabetes mellitus.
Lauster CD, McKaveney TP, Muench SV.
School of Pharmacy, University of Pittsburgh (UP).

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and role in therapy of vildagliptin for the treatment of type 2 diabetes mellitus were reviewed. SUMMARY: Vildagliptin is an agent in a new class of medications called dipeptidyl peptidase IV (DPP4) inhibitors. By inhibiting DPP4, vildagliptin causes an increase in glucagon like peptide-1 (GLP-1), an intestinal hormone that aids in glucose homeostasis and insulin secretion. The manufacturer of vildagliptin received an approvable letter from the Food and Drug Administration in late February 2007. Vildagliptin has a halflife of about 90 minutes; however, >/=50% of DPP4 inhibition continues for more than 10 hours, allowing for once- or twice-daily dosing. Clinical trials have shown that vildagliptin is effective in significantly lowering glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, and prandial glucose levels. Beta-cell function may also be improved. The most common adverse effects in patients receiving vildagliptin included headache, nasopharyngitis, cough, constipation, dizziness, and increased sweating. In most studies, the rate of hypoglycemia appeared to be similar to that of placebo. CONCLUSION: In clinical trials of patients with type 2 diabetes mellitus, vildagliptin has been shown to reduce HbA(1c), fasting plasma glucose levels, prandial glucose levels, and prandial glucagon secretion and to improve beta-cell function. If vildagliptin is approved for marketing, it will add to the available treatment options for diabetes and will provide patients and health care providers with another noninjectable therapy option.

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Diabetes Technol Ther. 2007 Jun;9(3):297-306.
Use of an Internet-Based Telemedicine System to Manage Underserved Women with Gestational Diabetes Mellitus.
Homko CJ, Santamore WP, Whiteman V, Bower M, Berger P, Geifman-Holtzman O, Bove AA.
Section of Cardiology, and Reproductive Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania., General Clinical Research Center, Department of Medicine, and Reproductive Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania., Department of Obstetrics, Gynecology, and Reproductive Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.

Background: Internet technology has been proven to be a successful tool for the management of patients with multiple medical conditions. The purpose of this study was to demonstrate the feasibility of monitoring glucose control in indigent women with gestational diabetes mellitus (GDM) over the Internet. Methods: Women with GDM were randomized to either the Internet group (n = 32) or the control group (n = 25). Patients in the Internet group were provided with computers and/or Internet access if needed. A website was established for documentation of glucose values and communication between the patient and the health care team. Women in the control group maintained paper logbooks, which were reviewed at each prenatal visit. Maternal feelings of diabetes self-efficacy were assessed at study entry and again before delivery. Results: Women in the Internet group accessed the system and sent on average 21.8 (+/- 16.9) sets of data. There was no difference between the two groups in regards either fasting or post-prandial blood glucose values, although more women in the Internet group received insulin therapy (31% vs. 4%; P <0.05). There were also no significant differences in pregnancy and neonatal outcomes between the two groups. Women in the Internet group demonstrated significantly higher feelings of self-efficacy at the study's end. Conclusions: The benefit of monitoring blood glucose in indigent women with GDM via the Internet was limited by their infrequent use of the telemedicine system. Although system use was not associated with improved pregnancy outcomes, women in the telemedicine group did experience enhanced feelings of diabetes psychosocial self-efficacy.

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Diabetes Technol Ther. 2007 Jun;9(3):241-5.
Evaluation of a Patient Education Booklet (SimpleStarttrade mark) Effect on Postprandial Glucose Control in Type 2 Diabetes.
King AB, Wolfe GS, Armstrong DU.
Diabetes Care Center, Salinas, California.

Background: Post-meal hyperglycemia is emerging as a cardiovascular risk factor and may be elevated despite a hemoglobin A1C (A1C) of <7%. The Simple Starttrade mark DVD (LifeScan, Milpitas, CA) was developed to educate patients about glycemic targets and dietary changes that could lessen glycemic excursions. We evaluated SimpleStart in a controlled, randomized, prospective trial using continuous glucose monitoring (CGM). Methods: Thirty subjects with type 2 diabetes mellitus having an A1C of <7.0% (mean 6.0%) were recruited from the Center's population. Subjects were randomized to either Simple Start DVD presentation and a 30-min diet education course (SS Group) or just the latter (Control Group). Subjects were seen at baseline and during weeks 6 and 12 by an investigator. Life-style and medication changes were advised based on history and self-monitored blood glucose downloaded meter data. CGM and A1C were done at baseline and during weeks 6 and 12. Results: Twenty-eight subjects completed the 12-week study with 14 subjects in the SS Group and Control Group being compared. There was no significant difference in the baseline or subsequent A1C levels or overall CGM glucose values between groups or over time. SMBG frequency was significantly increased in the SS Group from <1.0 per day to 2.0 per day (P < 0.001). At week 12, the mean glucose for the 4-h after-meal period was significantly lower in the SS Group than in the Control Group at breakfast and lunch in those subjects with adequate CGM tracings (P < 0.05). Conclusion: An educational program incorporating Simple Start facilitates patient behavioral changes, decreasing post-meal hyperglycemia.

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Diabetes Educ. 2007 May-Jun;33(3):475-82.
Obstructive sleep apnea, daytime sleepiness, and type 2 diabetes.
Chasens ER.
School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261, USA. chasense@pitt.edu

PURPOSE: The purpose of this article is to review the literature on obstructive sleep apnea, resultant daytime sleepiness, and type 2 diabetes mellitus, as the state of evidence exists. METHODS: A search was conducted on Medline and CINAHL using the search terms sleep apnea syndromes, obstructive sleep apnea, disorders of excessive somnolence, type 2 diabetes mellitus, and insulin resistance. This review includes only published research studies in English, in adults aged 19 years or older. There were 109 citations when the terms were combined, 36 citations that were identified as research studies, no randomized clinical trials, and only 1 qualitative study. RESULTS: Obstructive sleep apnea and type 2 diabetes share the risk factors of age and central abdominal obesity. Recent studies suggest that obstructive sleep apnea and type 2 diabetes not only frequently coexist but also have a bidirectional association wherein each condition exacerbates the other. The mechanism whereby obstructive sleep apnea affects glucose metabolism is likely repetitive hypoxia and sleep fragmentation, which cause a stress response with increased sympathetic nervous system activity, increased fatigue-causing cytokines, and altered leptin levels that result in weight gain. In addition, daytime sleepiness results in an impaired mood state that may impede diabetes management. CONCLUSIONS: Type 2 diabetes is prevalent in persons with obstructive sleep apnea, although the direction of causality is unknown. More research, including randomized clinical trials, is needed to determine how obstructive sleep apnea and daytime sleepiness affect persons with type 2 diabetes.

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Curr Med Res Opin. 2007 May 24; [Epub ahead of print]
A review of the effects of antihyperglycaemic agents on body weight: the potential of incretin targeted therapies.
Barnett A, Allsworth J, Jameson K, Mann R.

BACKGROUND: Current American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) treatment guidelines recommend metformin (which does not promote weight gain) as the first-line antihyperglycaemic drug for patients with type 2 diabetes. However, when metformin fails, the recommended add-on treatment options (sulphonylureas, glitazones and basal insulin) can lead to significant weight gain. This article reviews the effect on body weight of current treatments for type 2 diabetes and discusses the potential impact of weight gain in this patient group.Scope: MEDLINE searches were performed to evaluate the prevalence and impact of changes in body weight in type 2 diabetes (articles published between January 1966 and August 2006) and the effects of sulphonylureas, glitazones, insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors and incretin analogs on body weight in these patients (search between January 2004 and September 2006).FINDINGS: Weight gain in general affects not only the physiological capability of patients with diabetes to achieve glycaemic control, but also their psychological well-being, quality of life and persistence with antihyperglycaemic treatment. Excess body weight and obesity in patients with diabetes are also associated with increased healthcare resource utilisation. Development of obesity is also associated with increased cardiovascular risk, although a link between drug-induced weight gain per se and increased cardiovascular risk has not been established. Initial clinical trial experience with the new oral DPP-4 inhibitors such as sitagliptin and vildagliptin suggests that these agents are weight-neutral, while providing improved glycaemic control when added to metformin.CONCLUSIONS: Because currently available add-on treatments can cause weight gain, physicians initiating add-on therapy in patients who can no longer achieve glycaemic control with metformin are faced with the problem of improving glycaemic control while causing weight gain. Initial clinical trial experience with oral DPP-4 inhibitors such as sitagliptin and vildagliptin suggest that these agents may represent an important oral treatment option for weight-neutral, glycaemic control when added to metformin. The new oral DPP-4 inhibitors, therefore, represent a potentially important addition to the oral treatment options currently available for the management of type 2 diabetes mellitus. Long-term clinical trials are now required to evaluate the relative risk/benefit profile of these drugs compared with the established antihyperglycaemic drug classes.

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J Pediatr Endocrinol Metab. 2007 Apr;20(4):517-25.
Glycaemic control and hypoglycaemia in children, adolescents and young adults with unstable type 1 diabetes mellitus treated with insulin glargine or intermediate-acting insulin.
Herwig J, Scholl-Schilling G, Böhles H.
University Children's Hospital, Department of General Paediatrics I, Johann Wolfgang Goethe-University, Theodor-Stem-Kai 7, D 60590 Frankfurt, Germany. juergen.herwig@kgu.de

In this open study of clinical practice, 142 paediatric patients with type 1 diabetes mellitus (>1 year duration), stratified by age, received prandial insulin (regular or lispro) and either once daily insulin glargine (GLAR; n=74), titrated to target fasting blood glucose (FBG) levels 4.4-7.8 mmol/l, or NPH/semilente insulin (NPH insulin, administered once, twice or three times daily; n=68), titrated to target FBG 4.4-8.9 mmol/l. Both groups were treated for 20 +/- 10 months. HbA(1c) significantly increased in GLAR (7.3 +/- 1.0% to 7.6 +/- 1.1%; p = 0.003) and NPH/semilente insulin (7.7 +/- 1.6% to 8.3 +/- 1.5%; p = 0.0001) treated patients. The incidence of symptomatic hypoglycaemia was comparable between GLAR versus NPH/semilente insulin at endpoint (2.19 vs. 1.94 episodes/week); however, the overall incidence of severe hypoglycaemia was significantly lower with GLAR versus NPH/semilente insulin (0.14 vs. 0.73 events/patient-year; p = 0.002). The daily insulin dose was similar between the treatment groups; however, perceived quality of life (QoL) was better with GLAR. GLAR is associated with equivalent glycaemic control, less severe hypoglycaemia and improved QoL compared with NPH/semilente insulin.

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Diabetes Metab. 2007 Feb 20; [Epub ahead of print]
Continuous glucose monitoring in patients with type 2 diabetes: Why? When? Whom?
Monnier L, Colette C, Boegner C, Pham TC, Lapinski H, Boniface H.
Department of Metabolic Diseases, Lapeyronie Hospital, 34295 Montpellier cedex 05, France.

The overall assessment of glycaemic control in patients with type 2 diabetes should normally include the monitoring of three parameters that are usually depicted as the 'glucose triad': HbA(1c), fasting plasma glucose (FPG) and postprandial glucose (PPG) excursions. However one additional marker, the so-called 'glucose variability' might be as important as the three others since it has been demonstrated that both upward and downward glucose fluctuations are potent activators of oxidative stress. Even though many methods have been proposed for assessing glucose fluctuations, the 'mean amplitude glucose excursions' (MAGE) index remains the 'gold standard'. However MAGE estimation requires the use of continuous glucose sensors. Despite the debate on the reliability and cost of the devices that permit glucose monitoring, we suggest that interventional trials designed to evaluate the effects of glucose fluctuations on diabetic complications should benefit from the use of continuous glucose monitoring systems (CGMSs). More prosaically, the use of these technologies could be extended to current clinical care of type 2 diabetic patients especially for motivating them to accept earlier insulin treatments in case of 'oral antidiabetic drug secondary failure', and further for choosing the most appropriate insulin regimen.

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Diabetes Technol Ther. 2007 Feb;9(1):89-98.
Effect of standard (self-directed) training versus intensive training for lilly/alkermes human insulin inhalation powder delivery system on patient-reported outcomes and patient evaluation of the system.
Hayes RP, Nakano M, Muchmore D, Schmitke J.
Global Health Outcomes, Eli Lilly and Company, Indianapolis, Indiana.

Background: Inhaled insulin may provide patients with diabetes a safe, efficacious method of insulin delivery without the burden of injection, but complexity of and time required for training in proper use of delivery systems have not been evaluated. Methods: This 4-week, multicenter, single-blind, randomized parallel-group study compared the effect of self-directed [written text-graphic directions for use (DFU) with patient-assistance phone number] or intensive (same DFU, personal training by study personnel, inspiratory flow rate coaching) training for the Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system on patient-reported outcomes (PROs). Patients with type 2 diabetes poorly controlled on oral therapy (n = 102, mean hemoglobin A1C = 9.3%) were administered measures of vitality, diabetes-associated symptoms, fear of hypoglycemia, insulin-delivery system satisfaction, and a delivery system-specific evaluation questionnaire. Analysis of covariance models were used to compare the effect on PROs of treatment of diabetes for 1 month following the two training methods. Paired t tests were used to determine change in PROs after treatment with HIIP. Results: PROs did not differ significantly between training groups. Patients in both groups positively evaluated the delivery system, but the intensive group agreed significantly (P < 0.05) more strongly that the DFU was easy to follow. Improvements in vitality and symptoms of fatigue and increases in fear of hypoglycemia were detected among all patients after using HIIP (P < 0.05). Conclusion: Training for this HIIP delivery system can be self-directed without detrimental effects on PROs, making it potentially a more patient-friendly insulin-delivery method that should appeal to both clinicians and patients.

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Herz. 2007 Jan;32(1):51-57.
[Effects of Thiazolidinediones on Dyslipidemia in Patients with Type 2 Diabetes. Are All Equally Vasoprotective?]
[Article in German]
Haberbosch W.
SRH Zentralklinikum, Suhl, Deutschland.

Patients with type 2 diabetes face a high risk of cardiovascular morbidity and mortality. In these patients a whole cluster of cardiovascular risk factors is found, with insulin resistance being the most significant. Thiazolidinediones, in activating the peroxisome proliferator-activated receptor gamma, lower the insulin resistance.The two thiazolidinediones available at present, pioglitazone and rosiglitazone, do not differ in their effects on insulin resistance or glucose metabolism. They do, however, reveal very different effects on the dyslipidemia that is characteristic of diabetes, with elevated triglycerides, low high-density lipoprotein (HDL) and atherogenic small dense lipoprotein (LDL) cholesterol. Inter alia, data from a comparative study show that pioglitazone improves diabetic dyslipidemia more efficaciously than rosiglitazone. Despite similar effects on hyperglycemia (HbA1c reduction by 0.6% and 0.7%), both thiazolidinediones differ significantly in their effects on triglycerides (pioglitazone -51.9 mg/dl; rosiglitazone +13.1 mg/dl; p < 0.001), HDL cholesterol (pioglitazone +5.2 mg/dl; rosiglitazone +2.4 mg/dl; p < 0.001) and LDL cholesterol (pioglitazone +12.3 mg/dl; rosiglitazone +21.3 mg/dl; p < 0.001). LDL particle concentration was reduced with pioglitazone (n7.85%) and increased with rosiglitazone (+12%; p > 0.001).Only for pioglitazone the PROactive study, a major outcome trial, documented a significant reduction of cardiovascular outcomes. The principal secondary endpoint of death from any cause, nonfatal myocardial infarction (excluding silent myocardial infarction) or stroke was significantly reduced (16%; p = 0.027).The correlation of improved dyslipidemia, reconfirmed by PROactive, and cardiovascular prevention is yet to be resolved. However, as long as the vascular protective mechanism of pioglitazone is not conclusively resolved, findings may not be transmitted to other thiazolidinediones. For these substances, results from major outcome studies are to be required that prove a reduction of the cardiovascular risk.

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Arch Gerontol Geriatr. 2007;44 Suppl:61-7.
Diabetes and metabolic syndrome (MS).
Bellomo A, Mancinella M, Troisi G, Ettorre E, Marigliano V.
Department of Sciences of the Aging, University of the Studies in Rome "La Sapienza", Viale del Policlinico, 00161 Roma, Italy.

The MS is associated with increased morbidity and mortality for cardiovascular disease (CVD). MS is represented not only by metabolic alteration such as hyperglycemia, and hyperlipemia but also by a chronic pro-inflammatory state. Another responsible in the formation and progression of CVD is the so-called endothelial dysfunction, which is linked to insulin resistance itself. The common denominator of the MS is insulin resistance. The most convincing evidence for the existence of MS comes from the cluster analysis which outlines four main factors: the "metabolic factor", the "pressure factor", the "lipid factor" and the "obesity factor". It is clear that the presence of the MS appears to identify a substantial additional cardiovascular risk on top of the individual risk factors. The studies available in the literature have pointed out the beneficial effects, in terms of cardiovascular mortality, of the treatment with inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins): this reduction of risk has been observed despite the fact that high triglyceride and low high-density lipoprotein (HDL)-cholesterol levels, but not hypercholesterolemia, are the main features of the dyslipidemia observed in patients with MS. Yet, despite a normal low-density lipoprotein (LDL)-cholesterol level, patients with MS are at high risk for future CVD. For this reason, their treatment with statins is mandatory.

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Vasc Health Risk Manag. 2006;2(1):59-67.
Insulin glargine in the treatment of type 1 and type 2 diabetes.
Barnett AH.
Birmingham Heartlands Hospital, Undergraduate Centre, Birmingham, West Midlands, England, UK. anthony.barnett@heartofengland.nhs.uk

Insulin glargine is an analogue of human insulin that is modified to provide a consistent level of plasma insulin over a long duration. Pharmacokinetic and pharmacodynamic studies show that a single injection of insulin glargine leads to a smooth 24-hour time-action profile with no undesirable pronounced peaks of activity. In clinical trials, this profile has been associated with at least equivalent, if not better, glycemic control than other traditional basal insulins and a significantly lower rate of overall and nocturnal hypoglycemia. The convenience of a once-daily injection, a lack of need for resuspension (insulin glargine is a clear solution when injected), and lower rates of hypoglycemia should translate into improvements in patient treatment satisfaction. This review appraises the evidence for the view that insulin glargine represents an advance in basal insulin therapy for both type 1 and type 2 diabetes patients.

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Vasc Health Risk Manag. 2006;2(2):139-44.
The use of metoprolol CR/XL in the treatment of patients with diabetes and chronic heart failure.
De Freitas O, Lenz O, Fornoni A, Materson BJ.
Division of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida 33131, USA.

About 5 million Americans suffer from heart failure. Given the correlation of heart failure with age and the rising life expectancy, the prevalence of heart failure continues to increase in the general population. Sympathetic stimulation intensifies with progressive heart failure. The rationale to use beta-blockers in individuals with impaired myocardial function is based on experimental evidence supporting the notion that prolonged alpha- and beta-adrenergic stimulation leads to worsening heart failure. Until recently, safety concerns have precluded the use of beta-blockers in patients with diabetes and heart failure. However, several large, randomized, placebo-controlled clinical trials such as Metoprolol Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) have shown that beta-blockers can be safely used in patients with diabetes and heart failure. Moreover, beta-blockers significantly improved morbidity and mortality in this population. Based on this evidence, it is now recommended to add beta-blockers such as metoprolol CR/XL with an escalating dosage regimen to the treatment of patients with symptomatic heart failure who already are receiving a stable medical regimen including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, diuretics, vasodilators, or digitalis.

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Vasc Health Risk Manag. 2006;2(1):69-77.
Metabolic effects of the incretin mimetic exenatide in the treatment of type 2 diabetes.
Schnabel CA, Wintle M, Kolterman O.
Amylin Pharmaceuticals, Inc, 9360 Towne Centre Drive, Suite 110, San Diego, CA 92121, USA.

Interventional studies have demonstrated the impact of hyperglycemia on the development of vascular complications associated with type 2 diabetes, which underscores the importance of safely lowering glucose to as near-normal as possible. Among the current challenges to reducing the risk of vascular disease associated with diabetes is the management of body weight in a predominantly overweight patient population, and in which weight gain is likely with many current therapies. Exenatide is the first in a new class of agents termed incretin mimetics, which replicate several glucoregulatory effects of the endogenous incretin hormone, glucagon-like peptide-1 (GLP-1). Currently approved in the US as an injectable adjunct to metformin and/or sulfonylurea therapy, exenatide improves glycemic control through multiple mechanisms of action including: glucose-dependent enhancement of insulin secretion that potentially reduces the risk of hypoglycemia compared with insulin secretagogues; restoration of first-phase insulin secretion typically deficient in patients with type 2 diabetes; suppression of inappropriately elevated glucagon secretion to reduce postprandial hepatic output; and slowing the rate of gastric emptying to regulate glucose appearance into the circulation. Clinical trials in patients with type 2 diabetes treated with subcutaneous exenatide twice daily demonstrated sustained improvements in glycemic control, evidenced by reductions in postprandial and fasting glycemia and glycosylated hemoglobin (HbA(1c)) levels. Notably, improvements in glycemic control with exenatide were coupled with progressive reductions in body weight, which represents a distinct therapeutic benefit for patients with type 2 diabetes. Acute effects of exenatide on beta-cell responsiveness along with significant reductions in body weight in patients with type 2 diabetes may have a positive impact on disease progression and potentially decrease the risk of associated long-term complications.
 

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