Diabetes Research and Clinical Practice - Articles in Press

Patient perspectives on the role of weight management in type 2 diabetes - Corrected Proof

William H. Polonsky, Lawrence Fisher, Danielle Hessler — 2010-03-08

Abstract: Aims: To examine issues of weight misperception, perceived importance of weight management, and patient reports of their HCP's weight-related recommendations among patients with type 2 diabetes.Methods: 575 overweight adults with type 2 diabetes completed a survey that assessed perceptions about weight management and discussions with HCP's about weight issues.Results: Among patients with BMI>30, weight misperception was rare (<10%) and perceived importance of weight loss common (>85%). Among overweight patients with BMI<30, weight misperception was more common (47%) and importance of weight loss was endorsed less frequently (68%). Most patients reported that HCP's had advised weight loss (72%) and discussed weight issues at most visits (59%). However, recommendations from HCP's were rarely specific. Few were informed by HCP's that certain diabetes medications might make weight management difficult. Weight misperception was less common, importance of weight loss was more common and weight management efforts were more frequent when HCPs discussed these issues directly.Conclusions: Most overweight patients with type 2 diabetes recognize the importance of weight management. Patient reports indicate that HCP's are actively engaged in promoting weight loss and that their recommendations, when specific, are associated with patients’ more frequent weight management efforts.

Latent class analysis of the metabolic syndrome - Corrected Proof

2010-03-08

Abstract: Attempts to explain the associations among metabolic syndrome (MetS) features using factor analysis to identify unobserved potential causes have resulted in inconsistent findings. We examined whether an unobserved categorical factor explains the associations among MetS features using latent class analysis. A cross-sectional analysis of 499 non-diabetic Japanese-Americans who underwent measurements of fasting blood, waist circumference (WC) and CT-measured intra-abdominal fat (IAF) area was conducted. MetS components were defined by IDF criteria. IAF and fasting serum insulin (FI) were dichotomized at the 75th percentile. Latent two- and three-class models were fit that included hypertension, dyslipidemia, hyperglycemia, and either WC, IAF, or FI for a total of six models. A three-class latent model fit the data well, while a two-class model did not. In the three-class model, one latent class was strongly associated with all MetS components, while another was associated with hyperglycemia and hypertension only. IAF was associated with only one latent class. Latent class analysis supports the presence of an unobserved factor linked to the co-occurrence of MetS features. One class of this factor was associated with hypertension and hyperglycemia but not central adiposity or FI, suggesting another pathway for observed MetS features.

Predictors of diastolic dysfunction among minority patients with newly diagnosed type 2 diabetes - Corrected Proof

2010-03-02

Abstract: Aim: To determine mutable risk factors for asymptomatic diastolic dysfunction in ethnic minority patients newly diagnosed with type 2 diabetes.Methods: We recruited consecutive adults with newly diagnosed diabetes who had no signs or symptoms or history of heart disease. All patients received standardized evaluation including interview, physical examination, laboratory tests and echocardiogram with tissue Doppler studies. We used logistic regression models to identify mutable risk factors for diastolic dysfunction.Results: Among 126 study subjects (52% women, age 45±10 years, BMI 33±7, 42% with hypertension, 100% ejection fraction ≥50%), evidence of diastolic dysfunction was present in 64 (51%). After controlling for age, heart rate and blood pressure, independent predictors of diastolic dysfunction included physical inactivity (OR: 2.3; 95% CI: 0.9–6.1; P=0.08) and glucose (OR: 4.9; 95% CI: 1.4–17.8; P=0.02). Physical inactivity was associated with early diastolic dysfunction (impaired relaxation), whereas epicardial fat thickness and glucose levels were associated with late diastolic dysfunction (impaired compliance). The hs-CRP and BNP levels were not associated with diastolic dysfunction.Conclusions: Asymptomatic diastolic dysfunction was prevalent among urban minority patients newly diagnosed with diabetes. Important differences exist among factors that affect early and late diastolic function that may have prognostic and therapeutic implications.

Association between alcohol intake amount and prevalence of metabolic syndrome in Korean rural male population - Corrected Proof

2010-03-02

Abstract: Moderate alcohol consumption is known to be associated with a reduced risk of cardiovascular disease and mortality. However, few studies reported that long-term alcohol drinking may increase the prevalence of central obesity, and cardiovascular disease. We examined the association between metabolic syndrome, nutritional factors and alcohol intake amount in Korean male rural population.We performed a cross-sectional analysis on data from Korean Rural Genomic Cohort (KRGC) study. We used multiple logistic regression analysis to estimate the adjusted odds ratio of metabolic syndrome according to alcohol intake amount categories (never, 0–16g/day, 16–40g/day, and >40g/day).The age adjusted odds ratio for the prevalence of metabolic syndrome was significantly increased in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group (1.33; C.I., 1.11–1.59). These results were similar in the high energy intake group, but not in the low energy intake group. Waist circumference, blood pressure, and serum triglyceride levels were significantly higher in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group.These results suggest that large alcohol consumption is associated with metabolic syndrome and may be a modifiable risk factor of metabolic syndrome especially in subjects with high calorie intake.

Association between polymorphisms in human tumor necrosis factor-alpha (−308) and -beta (252) genes and development of gestational diabetes mellitus - Corrected Proof

Shabnam Montazeri, Sivalingam Nalliah, Ammu Kutty Radhakrishnan — 2010-03-02

Abstract: Objective: The aim of this study is to investigate if an association exists between single nucleotide polymorphism (SNP) in the tumor necrosis factor-alpha (TNF-α) and TNF-β genes.Methods: The DNA was extracted and SNP in the human TNF-α and TNF-β genes at positions −308 (G/A) and 252 (A/G), respectively, was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of TNF-α in different stages of pregnancy were quantified using enzyme linked immunosorbent assay (ELISA).Results: There was no significant difference in genotype and allele frequency of SNP at position −308 (G/A) in the promoter region of the human TNF-α gene as well as the SNP at position 252 (A/G) in the human TNF-β gene between the GDM and control subjects. Using the logistic regression model, it was found that the SNP in the TNF-α as well as TNF-β were not associated with development of GDM. In addition, the TNF-α levels in the plasma of GDM and control mothers were not significantly different.Conclusions: In the population studied, the SNP in position −308 (G/A) of the human TNF-α or in position 252 (A/G) of the human TNF-β gene is not an independent risk factor or a predictor for GDM.

The incorporation of family physicians in the assessment of diabetic retinopathy by non-mydriatic fundus camera - Corrected Proof

Romero Pedro, Sagarra Ramon, Ferrer Jeroni, Fernández-Ballart Juan, Baget Marc — 2010-03-02

Abstract: Aims: To evaluate the inclusion of family physicians in screening for diabetic retinopathy.Methods: We evaluated by non-mydriatic fundus camera 2779 diabetic patients. The family physicians made an initial evaluation of the fundus and pathological images were sent to a reference ophthalmologist. An audit was taken of all the patients at the end of the study. We analysed the concordance in: diabetic retinopathy, diabetic macular edema, and lesions in the macular area.Results: Diabetic retinopathy was observed in 226 patients (8.1%) and diabetic macular edema in 40 patients (1.4%). Other retinal pathologies were diagnosed in 291 (11.0%). The sensitivity of the study was 95.2% for diabetic retinopathy, 96.0% for macular lesions and 92.9% for diabetic macular edema. The specificity was above 98% in the three studied variables. Cohen's Kappa coefficient was 0.82 for diabetic retinopathy, 0.81 for diabetic macular edema and 0.96 for macular lesions.Conclusions: The inclusion of family physicians in the screening system seems to be effective in the diagnosis of diabetic retinopathy.

What happens after community-based screening for diabetes in rural and Indigenous individuals? - Corrected Proof

Richard T. Oster, Kelli Ralph-Campbell, Tracy Connor, Mary Pick, Ellen L. Toth — 2010-03-02

Abstract: Rural individuals (mostly Indigenous) were screened for undiagnosed diabetes and cardiovascular risk. A subsequent survey showed roughly half engaged in timely follow-up with the health care system. The Mobile Diabetes Screening Initiative identifies a substantial number of people needing medical attention, who may otherwise be “missed” through conventional healthcare delivery.

Prevalence and risk factors for albuminuria among type 2 diabetes mellitus patients: A Middle-East perspective - Corrected Proof

2010-03-02

Abstract: The aim of the study was to determine the prevalence and risk factors for albuminuria among 447 type 2 diabetic patients in three Gulf countries. Overall prevalence of albuminuria was 36%, which is similar to that reported in other DEMAND studies and was strongly related to poor glycemic control.

A new non-invasive technology to screen for dysglycaemia including diabetes - Corrected Proof

2010-02-26

Abstract: Objective: Assess the ability of a new device based on electrochemical principles using iontophoresis (the EZSCAN®) to detect impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM).Methods: Eligible Asian Indian subjects, n=212, had anthropometric and blood pressure measurements, followed by an OGTT, HbA1c, serum lipids tests and EZSCAN® measurement.Results: Biochemically, 24 subjects were diagnosed with DM, 30 with IGT, 57 subjects had normal glucose tolerance (NGT) with metabolic syndrome (MS) and 101 had NGT without MS. Fasting plasma glucose (FPG) and HbA1c levels were highest in the DM group (p<0.0001 for both). HDL-C levels were different (p=0.015). FPG at a cut-off level of 7.0mmol/L had a low sensitivity to detect DM (29%) EZSCAN® had a 75% sensitivity to detect DM, 70% for IGT and 84% for NGT with MS at threshold >50%.Conclusions: FPG had low sensitivity to detect DM in the study group. EZSCAN® demonstrated good sensitivity to detect IGT and DM and also identified NGT with MS. The concept of measuring ion fluxes through the skin appears to be a powerful method for early detection of MS, IGT and DM.

Identification of a common autoantigenic epitope of protein disulfide isomerase, golgin-160 and voltage-gated potassium channel in type 1 diabetes - Corrected Proof

Alessandra Fierabracci, Francesca Saura — 2010-02-19

Abstract: A common epitope of proteins golgin-160, voltage-gated potassium channel and disulfide isomerase was identified by screening with autoantibodies of a type 1 diabetic (T1D) patient a λUni-Zap cDNA library from human diabetic islets. The significance of the identified autoantigens to the disease pathogenesis remains to be elucidated.

Normalization of glucose intolerance in first-degree relatives of patients with type 2 diabetes - Corrected Proof

Mohsen Janghorban, Masoud Amini — 2010-02-18

Abstract: Aims: The aim of this study was to estimate the conversion rate to normal glucose tolerance (NGT) from a state of abnormal glucose metabolism and to identify characteristics predicting the conversion rate in first-degree relatives (FDRs) of patients with type 2 diabetes with glucose intolerance.Methods: A total of 2368 (614 men and 1754 women) FDRs of consecutive patients with type 2 diabetes aged 20–70 years in 2003–2005 were followed through 2007. Glucose tolerance classification was based on the criteria of the American Diabetes Association base on standard 75g 2-h oral glucose tolerance test. The study group consisted of 370 participants with glucose intolerance at baseline.Results: The conversion rates to normal glucose tolerance from impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were 16.2% (95% confidence interval (CI) 13.30, 19.10) and 10.9% (95% CI: 5.7, 16.1) per year after an average of 2 years, respectively. Lower baseline fasting plasma glucose (HR 1.02, 95% CI: 1.01, 1.04) and 2-h (HR 1.02, 95% CI: 1.01, 1.04) glucose predicted conversion to NGT, as did changes in body mass index (BMI), waist circumference (WC), and lipids.Conclusions: This is the first estimate of conversion rate and predictors from IFG and IGT to NGT in FDRs of people with type 2 diabetes in Iran. Lower baseline fasting, 2-h plasma glucose and changes in BMI, WC, and lipids predicted reversal to NGT at 24 months follow-up.

Prevalence of metabolic syndrome and optimal waist circumference cut-off points for adults in Beijing - Corrected Proof

2010-02-15

Abstract: Background: In the modified ATP III definition for metabolic syndrome (MS), the cut-off values for central obesity were set to ≥90cm for male and ≥80cm for women. Recently, a new Chinese definition for central obesity was set to ≥90cm for male and ≥85cm for women according to the corresponding BMI value of 25kg/m2.Objective: The purpose of this study was to explore the optimal WC cut-off points to reflect the cluster of multiple risk factors for adults in Beijing.Method: The data collected during the surveillance of risk factors for non-communicable diseases in Beijing 2005 were used, with a total of 16,711 adults studied. Subjects with two or more components from the modified ATP III definition other than central obesity were considered to have multiple risk factors.Results: The optimal WC cut-off points were 87cm in men and 80cm for women. When applied the WC advised definition for MS, the age-standardized prevalence was 38.0% for male and 32.3% for women, which is significantly higher than using the original one for men (34.7% vs 32.3%, P<0.001).Conclusion: The present study indicated that optimal waist circumference cut-off points were lower than that proposed in the modified ATP III definition, especially for men.

Six year weight change and type 2 diabetes among Australian Indigenous adults - Corrected Proof

Ming Li, Sandra Campbell, Robyn A. McDermott — 2010-02-11

Abstract: Aims: To estimate weight change over 6 years among Indigenous Australian adults and the association with incident diabetes in north Queensland.Methods: Baseline anthropometric measurements, behavioural factors, and blood samples were collected from 1674 Indigenous adults during 1999–2000 in 19 rural communities in north Queensland. Follow-up of 487 participants occurred during 2004–2007. Weight change was compared by age, sex, socioeconomic status, ethnicity, and behavioural factors. The association between weight change and diabetes incidence stratified by baseline BMI was studied using Cox's Proportional Hazard Model.Results: Significantly more weight was gained among younger participants (absolute interval weight gain: 12.5kg among 15–24 year olds, 5.1kg in 25–34 year olds, 3.4kg in 35–44 year olds, and 1.0kg in those over 45 years), and by those whose BMI was normal at baseline. Women were more likely than men to have substantial weight gain (43.3 vs 25.1%). Weight change was not associated with diabetes incidence but baseline obesity tripled the risk of developing diabetes (HR: 3.1, 95% CI: 1.6–6.1).Conclusions: Indigenous Australian adults studied here showed very high levels of weight gain over a short period. Interventions aimed at maintaining healthy weight, particularly among young Indigenous people are needed.

New diagnosis criteria for diabetes with hemoglobin A1c and risks of macro-vascular complications in an urban Japanese cohort: The Suita Study - Corrected Proof

2010-02-11

Abstract: The association of the new diagnosis criteria for diabetes adopting hemoglobin A1c, recently proposed by the international expert committee, with macro-vascular complications was tested in a 12-year population-based cohort. The present analysis suggested that this new criteria were applicable to macro-vascular complications in the Japanese.

Microinflammation is a common risk factor for progression of nephropathy and atherosclerosis in Japanese patients with type 2 diabetes - Corrected Proof

2010-02-08

Abstract: Aim: This study aimed to evaluate the change of serum levels of proinflammatory molecules in patients with type 2 diabetes and clarify the involvement of these molecules in diabetic nephropathy and atherosclerosis.Methods: Sixty-six Japanese type 2 diabetic patients (T2DM) and 39 healthy control subjects were enrolled. We assessed clinical parameters, urinary albumin excretion rate (AER), brachial-ankle pulse wave velocity (baPWV), intima media thickness (IMT) and serum levels of proinflammatory molecules.Results: Serum levels of IL-6, IP-10 and MCP-1 were significantly higher in T2DM than in control subjects. In T2DM, serum levels of high-sensitivity (hs) CRP, IP-10, hsTNF-α, VCAM-1 and E-selectin were positively correlated with AER. Serum levels of IP-10, hsTNF-α and VCAM-1 were positively correlated with baPWV. Serum levels of hsCRP, IL-6, IP-10 and hsTNF-α were positively correlated with IMT. Multiple linear regression analysis revealed that serum levels of hsTNF-α were independently associated with AER (β=0.235, P=0.038) and serum levels of IP-10 were independently associated with baPWV (β=0.209, P=0.047) and IMT (β=0.303, P=0.032).Conclusion: Our results suggest that low-grade inflammation, microinflammation, may be a common risk factor for diabetic nephropathy and atherosclerosis in Japanese type 2 diabetic patients.

Prescription of physical activity is not sufficient to change sedentary behavior and improve glycemic control in type 2 diabetes patients - Corrected Proof

2010-02-08

Abstract: Objective: To assess the impact of personalized exercise prescription on habitual physical activity and glycemic control in sedentary, insulin treated type 2 diabetes patients during a 2-y intervention period.Research design and methods: 74 patients were randomized to the intervention (n=38) or control (n=36) group. The intervention group was stimulated to increase daily physical activity through regular, structured, and personalized exercise prescription by a physical therapist over the 2-y intervention period.Results: Physical activity levels at work or in leisure time were not modulated by the exercise prescription intervention. In accordance, no changes in body composition, glycemic control, medication use or risk factors for cardiovascular disease were observed.Conclusions: Long-term behavioral intervention programs, providing individualized exercise prescription, are not sufficient to change sedentary behavior and/or improve glycemic control in insulin treated, type 2 diabetes patients.

Glucose control in patients with type 2 diabetes based on frequency of insulin glargine administration - Corrected Proof

Audrey K. Housel, Robert F. Shaw, Nancee V. Waterbury — 2010-02-08

Abstract: Glucose control and predictors of a switch from once to twice daily administration of insulin glargine in patients with type 2 diabetes was investigated. A mean decrease in %A1c of 0.52±0.12 (p=0.14) resulted, indicating clinical relevance. Daily dose was the only significant predictor of twice daily therapy.

Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy - Corrected Proof

2010-02-08

Abstract: Several studies found that adiponectin, an adipokine withstands atherosclerosis in vivo, is significantly increased in subjects with diabetic nephropathy (DN), but its clinical meaning remains unclear. For its structural similarity to complement C1q and collagen, we performed this study to explore the relationship between adiponectin and the vascular endothelial function alterations in DN patients. 50 type 2 diabetic patients without clinical cardiovascular complications were assigned to control group, microalbuminuria group (Micro-MA), and macroalbuminuria group (Macro-MA) according to the Mogensen's criteria. Plasma adiponectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) were detected. Flow-mediated dilatation (FMD), nitroglycerin-induced dilatation (NID) and cardiologic parameters were measured by ultrasound cardiogram. Plasma adiponectin level was significantly and gradually increased in agreement with the amount of urine albumin excretion. sVCAM-1 was higher in Micro-MA and Macro-MA patients than in the controls, but it was comparable between the former 2 groups. FMD and NID were both remarkably decreased in Macro-MA group compared with Micro-MA and control group. For the whole subjects, plasma adiponectin was negatively related to FMD (r=−0.397, P<0.01) and NID (r=−0.413, P<0.01). These results suggest that increased plasma adiponectin may predict co-existing vascular endothelial dysfunction in DN patients.

Three novel mutations in MODY and its phenotype in three different Czech families - Corrected Proof

2010-02-04

Abstract: Aims/hypothesis: MODY (Maturity Onset Diabetes of the Young) is an autosomal dominant inherited type of diabetes with significant genetic heterogeneity. New mutations causing MODY are still being found. A genetically confirmed diagnosis of MODY allows application of individualized treatment based on the underlying concrete genetic dysfunction. Detection of novel MODY mutations helps provide a more complete picture of the possible MODY genotypes.Materials and methods: We tested 43 adult Czech patients with clinical characteristics of MODY, using direct sequencing of HNF1A (hepatocyte nuclear factor 1-alpha), HNF4A (hepatocyte nuclear factor 4-alpha) and GCK (glucokinase) genes.Results: In three Czech families we identified three novel mutations we believe causing MODY—two missense mutations in HNF1A [F268L (c.802T>C) and P291S (c.871C>T)] and one frame shift mutation in GCK V244fsdelG (c.729delG). Some of the novel HNF1A mutation carriers were successfully transferred from insulin to gliclazide, while some of the novel GCK mutation carriers had a good clinical response when switched from insulin or oral antidiabetic drugs to diet.Conclusion: We describe three novel MODY mutations in three Czech families. The identification of MODY mutations had a meaningful impact on therapy on the mutation carriers.

Microvascular complications are associated with low levels of maternal sE-selectin and sVCAM-1 in pregnancy complicated with pregestational diabetes mellitus - Corrected Proof

Agnieszka Zawiejska, Ewa Wender-Ożegowska, Jacek Brązert — 2010-02-03

Abstract: Pregestational diabetes with vasculopathy in pregnant women is still associated with increased risk for severe maternal and foetal complications and their pathomechanism remains unclear. We investigate endothelial function in diabetic pregnant women with and without vascular disease, measured as changes in concentrations of soluble E-selectin and VCAM-1 throughout pregnancy. 121 pregnant women with PGDM and singleton pregnancy (30 participants with vasculopathy, 91 without vasculopathy) were enrolled into the prospective study. Control group consisted of 20 nondiabetic pregnant women in uncomplicated gestation, sampled cross-sectionally in early pregnancy and at term. We demonstrated lower concentrations of circulating sE-selectin both in early and in late diabetic gestation, irrespective of a concomitant vasculopathy. We also found reduced concentrations of sVCAM-1 in late gestation in diabetic pregnancies both with and without vascular disease, and reduced increase in its levels with gestation. We report significantly elevated concentrations of sVCAM-1 in early pregnancy in diabetic participants with retinopathy and nephropathy comparing with patients with retinopathy only and nondiabetic pregnant controls. We noted a general pattern of pregestational diabetes associated with reduced levels of cell adhesion molecules in early pregnancy with a further reduction during gestation, except for participants with combined retino- and nephropathy.

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.