Potential risk factors for diabetic neuropathy: a case control study

BACKGROUND: Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. METHODS: In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS) was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography). The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI), blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. RESULTS: Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, < 0.001 and 0.005). No correlation was found with any atherosclerosis risk factor (high BP, hyperlipidemia, cigarette smoking). CONCLUSION: In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort

Abstract Background Type 2 diabetes mellitus (T2D) is a leading cause of morbidity and mortality in Mexico. Here, we aimed to report incidence rates (IR) of type 2 diabetes in middle-aged apparently-healthy Mexican adults, identify risk factors associated to ID and develop a predictive model for ID in a high-risk population. Methods Prospective 3-year observational cohort, comprised of apparently-healthy adults from urban settings of central Mexico in whom demographic, anthropometric and biochemical data was collected. We evaluated risk factors for ID using Cox proportional hazard regression and developed predictive models for ID. Results We included 7636 participants of whom 6144 completed follow-up. We observed 331 ID cases (IR: 21.9 per 1000 person-years, 95%CI 21.37–22.47). Risk factors for ID included family history of diabetes, age, abdominal obesity, waist-height ratio, impaired fasting glucose (IFG), HOMA2-IR and metabolic syndrome. Early-onset ID was also high (IR 14.77 per 1000 person-years, 95%CI 14.21–15.35), and risk factors included HOMA-IR and IFG. Our ID predictive model included age, hypertriglyceridemia, IFG, hypertension and abdominal obesity as predictors (Dxy = 0.487, c-statistic = 0.741) and had higher predictive accuracy compared to FINDRISC and Cambridge risk scores. Conclusions ID in apparently healthy middle-aged Mexican adults is currently at an alarming rate. The constructed models can be implemented to predict diabetes risk and represent the largest prospective effort for the study metabolic diseases in Latin-American population

Analysis of the contribution of <it>FTO</it>, <it>NPC1, ENPP1, NEGR1, GNPDA2</it> and <it>MC4R</it> genes to obesity in Mexican children

<p>Abstract</p> <p>Background</p> <p>Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children.</p> <p>Methods</p> <p>The association of six European obesity-related SNPs in or near <it>FTO, NPC1, ENPP1, NEGR1, GNPDA2</it> and <it>MC4R</it> genes with risk of obesity was tested in 1,463 school-aged Mexican children (<it>N</it>_{<it>cases</it>} = 514; <it>N</it>_{<it>controls</it>} = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children.</p> <p>Results</p> <p>We found a significant effect of <it>GNPDA2</it> rs10938397 on risk of obesity (odds ratio [OR] = 1.30; <it>P</it> = 1.34 × 10^-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: <it>ENPP1</it> rs7754561, <it>MC4R</it> rs17782313 and <it>NEGR1</it> rs2815752. Importantly, the at-risk alleles of both <it>MC4R</it> rs17782313 and <it>NPC1</it> rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; <it>P</it> = 1.47 × 10^-3) and decreased fasting serum insulin levels (β = −0.10 μU/mL; <it>P</it> = 1.21 × 10^-3), respectively.</p> <p>Conclusion</p> <p>Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between <it>MC4R</it> and fasting glucose levels, and between <it>NPC1</it> and fasting insulin levels.</p