Diabetes Research and Clinical Practice - Articles in Press

Diabetes and sleep: A complex cause-and-effect relationship - Corrected Proof

Mark T.U. Barone, Luiz Menna-Barreto — 2010-09-01

Abstract: Strong associations of diabetes with sleep impairment have been frequently reported. In the present review, we discuss current evidence and hypotheses for how type 1 and type 2 diabetes mellitus are associated with sleep impairment. This association may be described as a vicious circle, where sleep disorders favor the development of type 2 diabetes or exacerbate the metabolic control of both types of diabetes, whereas diabetes itself, especially when associated with poor metabolic control, is often followed by sleep disorders. In this review, novel findings concerning the neuro-endocrine-metabolic mediation of the mentioned circle are highlighted. Understanding how this association occurs, the impact of sleep impairment on diabetes, and the impact of diabetes on the development or exacerbation of sleep disorders should lead to potential new therapeutic strategies for treating both conditions.

Fulminant type 1 diabetes mellitus with rhabdomyolysis: Have we overlooked the situation? - Corrected Proof

Zhimin Huang, Lijuan Xu, Fengzhen Li, Wanping Deng, Yanbing Li — 2010-08-30

Abstract: Fulminant type 1 diabetes mellitus (FT1DM) is characterized as remarkably abrupt onset and severe metabolic disorder. Prominent derangement of serum electrolytes was frequently observed, which could be associated with rhabdomyolysis. But the issue was not touched upon in most of the articles concerning FT1DM. Herein, we reported 2 cases. Since the clinical features of rhabdomyolysis vary, and creatine kinase levels are not routinely tested in young patients, the situation of rhabdomyolysis associated with FT1DM may be overlooked.

No association of the SUMO4 polymorphism M55V variant in type 2 diabetes in Iranian subjects - Corrected Proof

Soudabeh Fallah, Mehrzad Jafarzadeh, Mehdi Hedayati — 2010-08-23

Abstract: Introduction: Diabetes mellitus incidence has an increasing rate and it's genetic aspect is an important approach as a risk factor and predictive value in this disorder. In some population, SUMO4, a regulator of NF-κB, gene polymorphism is associated with diabetes. A single-nucleotide polymorphism was detected in SUMO4; substituting a highly conserved methionine with a valine residue (M55V). We studied the association between M55V polymorphism in the SUMO4 gene insusceptibility of type 2 diabetes in patients with type 2 diabetes.Materials and methods: Participants were 50 patients with type 2 diabetes and 50 control Iranian subjects. Genotyping was done using polymorphism chain reaction (PCR) technique and subsequent cleavage by restriction endonuclease (RFLP) for the M55V SUMO4 gene variant.Results: The frequency of SUMO4 AA, AG and GG were 13%, 25% and 12% in control group and 20%, 22%, 18% in the type 2 diabetes patients respectively. The SUMO4 M55V variant was not associated with the susceptibility of type 2 diabetes.Conclusion: The study indicates that the SUMO4 gene M55V variant was not associated with the susceptibility of the type 2 diabetes polymorphism.

Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus - Corrected Proof

2010-08-23

Abstract: Mitochondrial superoxide dismutase 2 (SOD2) is an endogenous anti-oxidant enzyme. The rs4880 gene variant results in a C>T substitution, influencing SOD enzymatic activity. This variant has been associated with micro- and macro-vascular complications in diabetes mellitus. Our aim was to examine the association between this variant and coronary heart disease (CHD) risk in a cross-sectional sample of subjects with diabetes.776 Caucasian subjects with diabetes were genotyped. CHD risk, oxidised-LDL and plasma total anti-oxidant status (TAOS) were analysed in relation to genotype. In females, the TT genotype was associated with CHD (CC/CT/TT: No CHD vs. CHD: 22.4/56.0/21.6% vs. 12.0/50.0/38.0%, p=0.03; for CC/CT vs. TT, p=0.01). The odds ratio for CHD associated with the TT genotype compared to CC/CT was 2.22 [95%CI: 1.17–4.24], p=0.01. The TT genotype was also associated with significantly lower plasma TAOS. In males, no association was observed between genotype and CHD risk, but CHD was significantly associated with age, lower HDL, higher triglycerides, higher BMI and cigarette smoking.The TT genotype of this variant is associated with increased CHD risk and lower plasma anti-oxidant defences in females with diabetes. This modest genotype-effect is not apparent in males where traditional risk factors may play a greater role.

Clinical approach to the patient with diabetes mellitus and very high insulin requirements - Corrected Proof

F. Ovalle — 2010-08-19

Abstract: A number of patients with diabetes require very high (>2Ukg−1day−1), or extremely high (>3Ukg−1day−1), insulin doses for the management of their hyperglycemia. Unfortunately, many of the physicians who treat these patients limit themselves to prescribing ever higher doses of insulin, without questioning why. Furthermore, when the insulin requirements get to be extreme, demanding an explanation, clinicians are frequently lost in a sea of literature where there is not a single paper dealing with this problem systematically.A systematic approach to the evaluation of these patients is necessary to facilitate an appropriate diagnosis, select the most reasonable therapy, and hopefully improve the long-term outcome of these patients. This manuscript intends to provide the clinician with a review of the literature pertinent for the differential diagnosis, work-up, and management of these patients.We will review the definitions of insulin sensitivity during normality, the various degrees or categories of insulin resistance, and the expected insulin requirements during each of these states. Subsequently, we propose a simple alphabetic mnemonic approach to help remember the differential diagnosis, and a clinical algorithm to help guide the work-up of these patients. Lastly, we briefly discuss general management considerations in these conditions.

DPP-4 inhibitors: What may be the clinical differentiators? - Corrected Proof

John Gerich — 2010-08-16

Abstract: Attenuation of the prandial incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), contributes to hyperglycemia in type 2 diabetes mellitus (T2DM). Since the launch of sitagliptin in 2006, a compelling body of evidence has accumulated showing that dipeptidyl peptidase-4 (DPP-4) inhibitors, which augment endogenous GLP-1 and GIP levels, represent an important advance in the management of T2DM. Currently, three DPP-4 inhibitors – sitagliptin, vildagliptin and saxagliptin – have been approved in various countries worldwide. Several other DPP-4 inhibitors, including linagliptin and alogliptin, are currently in clinical development. As understanding of, and experience with, the growing number of DPP-4 inhibitors broadens, increasing evidence suggests that the class may offer advantages over other antidiabetic drugs in particular patient populations. The expanding evidence base also suggests that certain differences between DPP-4 inhibitors may prove to be clinically significant. This therapeutic diversity should help clinicians tailor treatment to the individual patient, thereby increasing the proportion that safely attain target HbA1c levels, and reducing morbidity and mortality. This review offers an overview of DPP-4 inhibitors in T2DM and suggests some characteristics that may provide clinically relevant differentiators within this class.

Cost-effectiveness of administering oral adsorbent AST-120 to patients with diabetes and advance-stage chronic kidney disease - Corrected Proof

2010-08-16

Abstract: Aims: AST-120, an oral adsorbent currently on-label only in Asian countries with phase III trials ongoing in the US, slows renal disease progression in patients with diabetes and advanced-stage chronic kidney disease (CKD). The objective of this study is to evaluate the cost-effectiveness of using AST-120 to treat patients with type 2 diabetes and advanced-stage CKD.Methods: We used Markov model simulating the progression of diabetic nephropathy. Data were obtained from randomized trials estimating the progression of diabetic nephropathy with and without AST-120, and published literature. The base population was patients 60 years of age with type 2 diabetes and Stages 3 and 4 CKD.Results: Treating patients with diabetes and advanced-stage CKD was found to be a dominant strategy, and quality of life improved further and more money was saved (0.22 quality-adjusted life years [QALYs] and $15,019 per patient) using AST-120 than the control strategy. Sensitivity analysis results were robust with regard to cost, adherence, and quality of life associated with AST-120 therapy, as well as age at diagnosis. The model was relatively sensitive to the effectiveness of AST-120.Conclusions: Treating patients with type 2 diabetes and advanced-stage CKD with AST-120 appears to extend life and reduce costs.

Increased red cell count in diabetes and pre-diabetes - Corrected Proof

D. Simmons — 2010-08-11

Abstract: The aim of this study was to test whether an increased red cell count (RCC) is present in pre-diabetes, obesity and the metabolic syndrome. The results demonstrate that these diabetes precursor states are associated with an increased RCC. This relationship can be explained, in part, by an increased HbA1c.

Glucose intolerance and cardiovascular risk factors in Hong Kong: Data from two occupation-based cross-sectional surveys - Corrected Proof

2010-08-02

Abstract: Aims: To examine the distribution of plasma glucose and related cardiovascular risk factors in two occupation-based cross-sectional surveys in a Chinese ethnic population.Methods: Two cross-sectional surveys in a Hong Kong working population. In 1990, 1496 participants aged 18–66 years underwent an OGTT, anthropometric, and other biochemical measures. Identical measures were collected from 534 participants aged 20–72 years in 2001–2003. Data were direct age-standardised to compare CVD risk factor prevalence. Linear regression modelling was used to examine the distribution of continuous CVD risk factors.Results: Mean (SD) 2-h plasma glucose values were 5.6mmol/l (2.1) in 1990 and 6.5mmol/l (2.5) in 2001–2003, an apparent increase of 0.5mmol/l (95% CI 0.3 to 0.7, p<0.001) after age and sex adjustment. However, there was no significant difference in the age-standardised prevalence of glucose intolerance, overweight or obesity. There were significantly smaller proportions of women with hypertension and hyperlipidaemia and male smokers in the second compared to the first survey.Conclusions: We observed a relatively adverse glycaemia profile, which may have worsened over time, in two healthy populations of survey respondents, with comparatively low rates of most CVD risk factors. This has implications for the future burden of disease associated with hyperglycaemia in this population.

Depression and hemoglobin A1c in type 1 and type 2 diabetes: The role of self-efficacy - Corrected Proof

William P. Sacco, Cathy A. Bykowski — 2010-07-30

Abstract: Aims: To examine a self-efficacy explanation of the finding that depression is related to hemoglobin A1c (A1c) level in people with type 1 but not type 2 diabetes.Methods: Cross-sectional design involving 124 participants with type 1 (n=32) and type 2 (n=92) diabetes. Participants completed measures of depression and diabetes-related self-efficacy. A1c was obtained from medical records.Results: Replicating prior findings, A1c was significantly correlated with depression in type 1 participants (r=.51, p<.01), but not in type 2 participants (r=.11, ns). As hypothesized, A1c was significantly correlated with self-efficacy among type 1 participants (r=−.42, p<.05) but not among type 2 participants (r=−.01, ns). Self-efficacy also mediated the effect of A1c on depression among the type 1 participants (Z=2.21, p<.05).Conclusion: In people with type 1, but not type 2 diabetes, A1c levels are related to diabetes adherence mastery (self-efficacy), which mediates the link between A1c and depression. Results are discussed with regard to the proposal that perceptions of ineffective control over one's health play a role in the development of depression (a consequence model of depression in diabetes).

Safety and tolerability of vildagliptin vs. thiazolidinedione as add-on to metformin in type 2 diabetic patients with and without mild renal impairment: A retrospective analysis of the GALIANT study - Corrected Proof

M.A. Banerji, D. Purkayastha, B.H. Francis — 2010-07-26

Abstract: Objective: This retrospective analysis assessed safety and tolerability of vildagliptin (Vilda) as an add-on to metformin in type 2 diabetes mellitus (T2DM) patients with normal renal function (GFR >80mL/min/1.73m2) and mild renal impairment (GFR: >50 to ≤80mL/min/1.73m2).Methods: Adverse events (AE) from this 12-week, randomized, open-label study comparing Vilda 100mg and thiazolidinediones (TZD) as an add-on therapy in patients with T2DM inadequately controlled (HbA1c: 7–10%) on a stable dose of metformin (≥1000mg/day) were analyzed.Results: Of 2627 randomized patients, 1278 in the Vilda and 635 in the TZD groups had normal renal function; 463 in the Vilda and 230 in the TZD groups had mild renal impairment. Higher incidence of headache and rash was noted in both Vilda groups, whereas those with mild renal impairment receiving TZD experienced a higher incidence of peripheral edema and URI. Fewer patients in the Vilda group discontinued the study due to AEs compared to TZD group. Serious AEs were greater in TZD groups (normal: 2.4%; mild renal impairment: 3.0%) compared to Vilda groups (normal: 1.6%; mild renal impairment: 2.4%).Conclusion: The safety profile of Vilda or TZD as an add-on to metformin was similar in patients with mild renal impairment and normal renal function.

Behavioral strategies in diabetes prevention programs: A systematic review of randomized controlled trials - Corrected Proof

2010-07-26

Abstract: The worldwide epidemic of type 2 diabetes (T2D) emphasizes the need for guidelines regarding community implementation of lifestyle modification prevention programs. An understanding of effective behavioral strategies is needed if evidence translation is to be realized. The aim of this paper is to systematically review the behavioral change strategies for lifestyle T2D prevention programs.Methods: Randomized controlled trials (RCTs) of lifestyle interventions for the prevention of T2D were reviewed with a systematic literature search. Data relating to the behavioral strategies and trial outcomes were extracted.Results: Overall, lifestyle interventions were successful in reducing the incidence of T2D. The behavioral strategies utilized in these interventions were drawn from a variety of theoretical backgrounds. All RCTs utilized intensive modes of delivery and were associated with low dropout rates of 5.5–13.4%.Conclusions: The available evidence shows that a robust behavioral change strategy is an essential part of an effective lifestyle modification program, as the absence of intensive individualized advice or “information only” more closely resembles the control group interventions used in these RCTs.

Predictors of success to weight-loss intervention program in individuals at high risk for type 2 diabetes - Corrected Proof

2010-07-26

Abstract: This study aimed at identifying predictors of success (retention after one year of intervention with ≥5% weight loss) in subjects at high risk for type 2 diabetes enrolled in a lifestyle modification program. Fifty-one individuals with BMI ≥27kg/m2 and pre-diabetes or metabolic syndrome were enrolled in an individualized multidisciplinary lifestyle intervention to induce weight loss. Subjects were assessed initially with a 16-item weight-loss readiness tool (WLRT) based on stages of change model; a 6-min walk test; and anthropometric measures. The most significant independent factor associated with no success was a lower result to the question “I am capable of doing more physical activity” (P=0.001). The second significant independent predictor was ≤0.5% weight loss 6 weeks after initiating intervention (P=0.01). Excluding subjects with both criteria would have reduced by 52% the number of subjects eligible for the program, decreased the dropout rate from 30% to 17%, and increased the proportion of subjects with ≥5% weight loss at one year from 51% to 80%. Importantly, only 4% of subjects would have been falsely identified as non-responders. These results indicate that a practical WLRT, in combination with early weight-loss response, is helpful to identify subjects with greater chances of success to lifestyle intervention.

Comment on: “Evaluation and comparison of guidelines for the management of people with type 2 diabetes from eight European countries” by Stone et al. on behalf of the GUIDANCE study group (Diabetes Res Clin Pract. 2010; 87(2): 252–60) - Corrected Proof

Johan Wens, Paul Van Royen — 2010-07-20

Abstract: The authors compared eight national type 2 diabetes guidelines for key process and outcome indicators. The comparison was performed after accurate selection, and quality of the different guidelines was assessed by means of the AGREE instrument, developed to address the issue of variability in guideline quality. Unless this precise methodological description some concerns remain after reading the paper.

2010 Consensus statement on the worldwide standardization of the hemoglobin A1c measurement - Corrected Proof

Ragnar Hanas, Garry John — 2010-07-02

Glycated hemoglobin concentrations (most commonly hemoglobin A1c; HbA1c) reflect time averaged blood glucose during the previous 2–3 months, and are used as the gold standard for long-term follow-up of glycemic control. Standardization with common calibration was first proposed in 1984 . It was only after the publication of the DCCT study in 1993 , however, that the issue of international standardization of HbA1c measurements became an important objective for scientists and clinicians. At that time, the lack of international standardization resulted in several countries developing national standardization programs; most notable of these are:

Angiotensin converting enzyme inhibitor or angiotensin II receptor blocker for the prevention of type 2 diabetes mellitus? - Corrected Proof

Ching-Chu Chen, An-Na Chiang, Min-Huang Hsieh — 2010-07-01

Previous large-scale clinical studies showed that the incidence of new onset diabetes was lower in people treated with either angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) than individuals treated with other anti-hypertensive drugs or placebo . These promising observations, especially the HOPE trial (ramipril vs placebo, 30% reduction in the new onset of diabetes, p<0.001 in the post hoc analysis), led to the initiation of ramipril to prevent the development of diabetes in subjects with impaired fasting glucose . However, the ramipril trial failed to reduce the incidence of diabetes . In contrast, a recent prospective, large-scale, double-blind, placebo controlled study reported that valsartan significantly lowered the incidence of new-onset of diabetes in subjects with impaired glucose tolerance . Why ramipril did not have a similar effect in reducing the incidence of diabetes as valsartan is currently unknown. Here, we report different effect on the activation of PPARγ between ACEI and ARB, which may offer part of the explanation for the differences between these two drugs in preventing diabetes in people with hypertension and impaired fasting glucose or impaired glucose tolerance. The detailed description of the methods for measurement of PPARγ activation and glucose uptake was reported in our previous study . In brief, for the measurement of PPARγ activation, HuH-7 cells were transiently transfected with 0.5μg of PPREγ reporter constructs and 0.1μg of cytomegalovirus-β-galactosidase vector (pCMV-β-Gal). After transfection, HuH-7 cells were incubated in the presence of solvent alone (served as control) or varying doses of ACEI or ARB for 24h. A 2μM rosiglitazone was used as a positive control. The luciferase activity of PPREγ reporter plasmid-transfected cells divided by the β-galactosidase activity of pCMV-β-Gal-transfected cells represents the relative PPARγ activation of each experiment. As shown in figure, losartan and irbesartan instead of ramipril and imidapril significantly elevated PPARγ activation in various doses in HuH-7cells. We further used 2-deoxy-d-[3H] glucose to evaluate the glucose uptake effect of irbesartan. We found that compared with the control group, irbesartan at concentrations of 8μM (546.1±70.7dpm vs 476.9±257.9dpm, p<0.05) and 10μM (725.9±367.7dpm vs 476.9±257.9dpm, p<0.05) significantly increased the level of glucose uptake in 3T3-L1 cells. In conclusion, ARB increased PPARγ activation and stimulated glucose uptake. Lack of the effect on the PPARγ activation in ACEI maybe the explanation for the negative result of the ramipril study ().

Factors related to insulin resistance in type 1 diabetic patients treated with intensive insulin therapy from the onset of the disease - Corrected Proof

2010-06-11

Insulin resistant (IR) has been recently suggested to increase the risk of late diabetic complications in type 1 diabetes (DM1) . Moreover, it has been shown that IR is a strong predictor of mortality in DM1 . Thus, the aim of the study was to assess the predictors of IR in type 1 diabetic patients.

Diabetic kidney disease: Act now or pay later - Corrected Proof

2009-12-31

In 2003, the International Society of Nephrology and the International Diabetes Federation launched a booklet called “Diabetes and Kidney Disease: Time to act” to highlight the global pandemic of type 2 diabetes and diabetic kidney disease. It aimed to alert governments, health organisations, providers, doctors and patients to the increasing health and socio-economic problems due to diabetic kidney disease and its sequelae, end stage kidney disease requiring dialysis and cardiovascular death. Seven years later, the same message has become even more urgent. World Kidney Day 2010, under the auspices of the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF), together with the International Diabetes Federation (IDF), provides yet another chance to underline the importance of diabetic kidney disease, stress its lack of awareness at both public and government levels and emphasise that its management involves prevention, recognition and treatment of its complications. Primary prevention of type 2 diabetes will require massive lifestyle changes in the developing and developed world supported by strong governmental commitment to promote lifestyle and societal change.