Incidence of proteinuria in type 2 diabetes mellitus in the Pima Indians

Incidence of proteinuria in type 2 diabetes mellitus in the Pima Indians. Little is known of the natural history of nephropathy in type 2 (non-insulin-dependent) diabetes, yet type 2 diabetes is a major cause of end-stage renal disease in the United States. The incidence rate of heavy proteinuria was determined in Pima Indians participating in a longitudinal population study of diabetes and its complications. Heavy proteinuria was defined by a urine protein (g/liter) to urine creatinine (g/liter) ratio ≥ 1.0 (≥ 113mg protein/mmol creatinine), a level which corresponds to a urine protein excretion rate of about 1 g/day. The incidence rates of proteinuria in diabetic Pimas were 4, 12, 37, and 106 cases/1,000 person-years at risk in the periods 0 to 5, 5 to 10, 10 to 15, and 15 to 20 years after the diagnosis of diabetes. The cumulative incidence rates were 2%, 8%, 23%, and 50% at 5, 10, 15, and 20 years, respectively. The duration of diabetes, severity of diabetes as determined by the degree of hyperglycemia and type of treatment, and blood pressure were risk factors for proteinuria. The presence of heavy proteinuria was strongly associated with the development of renal insufficiency, defined by serum creatinine ≥ 2.0 mg/dl (≥ 177 µmol/liter). The incidence of proteinuria in type 2 diabetes in Pima Indians was as high as that reported in type 1 diabetes in other populations and represents a frequent, serious complication of the disease

Treatment-Induced Changes in Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion in the Diabetes Prevention Program Cohort.

BACKGROUND AND OBJECTIVES: Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity. DESIGN, SETTING, PARTICIPANTS AND METHODS: We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) and plasma adiponectin concentration were available in 2553 subjects. RESULTS: Adjusting for age, sex and race/ethnicity, we observed a statistically significant but weak inverse relationship between adiponectin and ACR at baseline (conditional Spearman\u27s rho = (-) 0.04, p = 0.04). Although DPP treatments significantly increased plasma adiponectin, there were no treatment effects on ACR and no differences in ACR across treatment groups. There was a weak direct (not inverse) association between change in adiponectin and change in albuminuria (adjusted Spearman\u27s rho = (+) 0.04, p = 0.03). CONCLUSIONS: In a large, well-characterized cohort of obese dysglycemic subjects we observed a weak inverse association between circulating adiponectin concentrations and urinary albumin excretion at baseline. Contrary to the hypothesized effect, treatment-related increases in plasma adiponectin were not associated with a reduction in ACR. The association of change in adiponectin with change in ACR should be assessed in populations with overt albuminuria before excluding a beneficial effect of increasing adiponectin to reduce ACR in obesity

Genetic Admixture and Gallbladder Disease in Mexican Americans

Gallbladder disease is a common source of morbidity in the Mexican American population. Genetic heritage has been proposed as a possible contributor, but evidence for this is limited. Because gallbladder disease has been associated with Native American heritage, genetic admixture may serve as a useful proxy for genetic susceptibility to the disease in epidemiologic studies. The objective of our study was to examine thepossibility that gallbladder disease is associated with greater Native American admixture in Mexican Americans. This study used data from the Hispanic Health and Nutrition Examination Survey and was based on 1,145 Mexican Americans who underwent gallbladder ultrasonography and provided usable phenotypic information. We used the GM and KM immunoglobulin antigen system to generate estimates of admixture proportions and compared these for individuals with and without gallbladder disease. Overall, the proportionate genetic contributions from European, Native American, and African ancestries in our sample were 0.575, 0.390, and 0.035, respectively. Admixture proportions did not differ between cases and noncases: Estimates of Native American admixture for the two groups were 0.359 and 0.396, respectively, but confidence intervals for estimates overlapped. This study found no evidence for the hypothesis that greater Native American admixture proportion is associated with higher prevalence of gallbladder disease in Mexican Americans. Reasons for the finding that Native American admixture proportions did not differ between cases and noncases are discussed. Improving our understanding of the measurement, use, and limitations of genetic admixture may increase its usefulness as an epidemiologic tool as well as its potential for contributing to our understanding of disease distributions across populations

Non‐Insulin Dependent Diabetes Mellitus and Alveolar Bone Loss Progression Over 2 Years

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141702/1/jper0076.pd

Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program

OBJECTIVE—To assess the association between elevated depression symptoms or antidepressant medicine use on entry to the Diabetes Prevention Program (DPP) and during the study and the risk of developing diabetes during the study. RESEARCH DESIGN AND METHODS—DPP participants (n = 3,187) in three treatment arms (intensive lifestyle [ILS], metformin [MET], and placebo [PLB]) completed the Beck Depression Inventory (BDI) and reported their use of antidepressant medication at randomization and throughout the study (average duration in study 3.2 years). RESULTS—When other factors associated with the risk of developing diabetes were controlled, elevated BDI scores at baseline or during the study were not associated with diabetes risk in any arm. Baseline antidepressant use was associated with diabetes risk in the PLB (hazard ratio 2.25 [95% CI 1.38–3.66]) and ILS (3.48 [1.93–6.28]) arms. Continuous antidepressant use during the study (compared with no use) was also associated with diabetes risk in the same arms (PLB 2.60 [1.37–4.94]; ILS 3.39 [1.61–7.13]), as was intermittent antidepressant use during the study in the ILS arm (2.07 [1.18–3.62]). Among MET arm participants, antidepressant use was not associated with developing diabetes. CONCLUSIONS—A strong and statistically significant association between antidepressant use and diabetes risk in the PLB and ILS arms was not accounted for by measured confounders or mediators. If future research finds that antidepressant use independently predicts diabetes risk, efforts to minimize the negative effects of antidepressant agents on glycemic control should be pursued

The prevention of type 2 diabetes

Type 2 diabetes mellitus (T2DM) affects more than 7% of adults in the US and leads to substantial personal and economic burden. In prediabetic states insulin secretion and action—potential targets of preventive interventions—are impaired. In trials lifestyle modification (i.e. weight loss and exercise) has proven effective in preventing incident T2DM in high-risk groups, although weight loss has the greatest effect. Various medications (e.g. metformin, thiazolidinediones and acarbose) can also prevent or delay T2DM. Whether diabetes-prevention strategies also ultimately prevent the development of diabetic vascular complications is unknown, but cardiovascular risk factors are favorably affected. Preventive strategies that can be implemented in routine clinical settings have been developed and evaluated. Widespread application has, however, been limited by local financial considerations, even though cost-effectiveness might be achieved at the population level

Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program

OBJECTIVE: We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss–inducing interventions (lifestyle and metformin) versus placebo. RESEARCH DESIGN AND METHODS: Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end). RESULTS: Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (−0.63 and −0.93 kg/allele, P ≤ 0.005, respectively). Gene–treatment interactions were observed for short-term (LYPLAL1 rs2605100, P$_{lifestyle*SNP}$ = 0.032; GNPDA2 rs10938397, P$_{lifestyle*SNP}$ = 0.016; MTCH2 rs10838738, P$_{lifestyle*SNP}$ = 0.022) and long-term (NEGR1 rs2815752, P$_{metformin*SNP}$ = 0.028; FTO rs9939609, P$_{lifestyle*SNP}$ = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P$_{lifestyle*SNP}$ < 0.05). CONCLUSIONS: Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention