Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.

Aim. This study compares the usefulness of Montreal Cognitive Assessment (MoCA) to Standardized Mini-Mental Status Exam (SMMSE) for diagnosing mild cognitive impairment (MCI) in Type 2 diabetes mellitus (DM) population. Methods. This prospective pilot study enrolled 30 community dwelling adults with Type 2 DM aged 50 years and above. Subjects were assessed using both the SMMSE and MoCA for MCI. In all subjects, depression and dementia were ruled out using the DSM IV criteria, and a functional assessment was done. MCI was diagnosed using the standard test, the European consortium criteria. Sensitivity and specificity analysis, positive and negative predictive values, likelihood ratios and Kappa statistic were calculated. Results. In comparison to consortium criteria, the sensitivity and specificity of MoCA were 67% and 93% in identifying individuals with MCI, and SMMSE were 13% and 93%, respectively. The positive and negative predictive values for MoCA were 84% and 56%, and for SMMSE were 66% and 51%, respectively. Kappa statistics showed moderate agreement between MoCA and consortium criteria (kappa = 0.4) and a low agreement between SMMSE and consortium criteria (kappa = 0.07). Conclusion. In this pilot study, MoCA appears to be a better screening tool than SMMSE for MCI in the diabetic population.

OBJECTIVES: Pharmacologic evidence suggests adequate antiplatelet activity in diabetic patients requires >100 mg aspirin daily, yet recent trials have used ≤100 mg daily. This meta-analysis explored the relationship between aspirin dose and prevention of cardiovascular events. DATA SOURCES: Six electronic databases were searched using database-appropriate terms for aspirin, diabetes, and comparative study from inception until February 2010. REVIEW METHODS: Randomized controlled trials and cohort studies comparing aspirin to no antiplatelet therapy were included if they reported cardiovascular events as pre-specified outcomes, aspirin dose, and number of diabetic patients. Studies were stratified by daily aspirin dose (≤100 mg; 101-325 mg; >325 mg) and pooled risk ratios (RR) were calculated using random effects models. All-cause mortality was the primary outcome of interest. Cardiovascular-related mortality, myocardial infarction, and stroke were secondary outcomes. RESULTS: Data for diabetic patients were available from 21 studies (n=17,522). Overall, 1,172 (15.4%) of 7,592 aspirin users and 1,520 (18.4%) of 8,269 controls died (p=0.31). The pooled RRs were 0.89 (95% CI: 0.72-1.10; p=0.27) from 13 studies using ≤100 mg (I 2 =64%); 0.89 (95% CI: 0.61-1.30; p=0.55) from four studies using 101-325 mg (I 2 =83%); and 0.96 (95% CI: 0.85-1.08; p= 0.50) from eight studies using >325 mg (I 2 =0%). Aspirin use was associated with a significantly lower risk of mortality (RR: 0.82; 95% CI: 0.69-0.98; p=0.03) in 13 secondary prevention studies (I 2 =27%), whereas aspirin use in seven primary prevention studies (I 2 =0%) was not (RR: 1.01; 95% CI 0.85-1.19; p=0.94). A substantial amount of heterogeneity was observed amongst studies in all outcomes. Although inclusion of cohort studies was a major source of heterogeneity, stratification by study design did not reveal a significant dose-response relationship. CONCLUSIONS/INTERPRETATION: This summary of available data does not support an aspirin dose-response effect for prevention of cardiovascular events in diabetic patients. However, the systematic review identified an important gap in randomized controlled trial evidence for using 101-325 mg aspirin daily in diabetes.

Hypoglycemia is a common clinical problem in elderly patients with diabetes. Aging modifies the counterregulatory and symptomatic responses to hypoglycemia. Hypoglycemia in the elderly is not only due to tight blood sugar control, but also due to a multitude of other factors. Hypoglycemia often occurs with insulin, sulfonylureas, or meglitinide therapy. However, other causes may also contribute to hypoglycemia, such as decreased cognition, renal impairment, or polypharmacy. The presenting features of hypoglycemia may be atypical and misinterpreted, resulting in delayed treatment. Morbidity is greater in elderly patients, and the risk of progression to severe hypoglycemia is high because of their altered symptom profile, diminished symptom intensity, and altered glycemic thresholds. Hypoglycemia seems to be the main limiting factor in their glycemic control. In this article we discuss strategies to prevent hypoglycemic episodes.

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Genetic factors contribute to the development of NIDDM, and genes involved in regulating pancreatic beta-cell function and insulin's effects on glucose metabolism are good candidates for being NIDDM susceptibility loci. However, testing candidate genes for linkage to NIDDM depends on the identification of highly informative DNA polymorphisms in or near the candidate locus. Here we describe an approach for identifying highly polymorphic markers near candidate genes that utilizes the emerging physical map of the human genome. A sequence-tagged site from the candidate gene is used to screen the Centre d'Etude du Polymorphisme Humain megabase-insert yeast artificial chromosome library, which contains information on the physical localization of >3,000 genetically mapped simple sequence repeat DNA polymorphisms. Thus, identification of a yeast artificial chromosome containing the candidate locus will in many instances also identify a physically linked simple sequence repeat DNA polymorphism that can be used as a marker for the candidate gene in linkage studies. We have used this approach to identify a marker for the islet amyloid polypeptide gene on chromosome 12. The physical mapping of this gene to a yeast artificial chromosome showed that it was in the same yeast artificial chromosome as the gene encoding liver glycogen synthase, another possible NIDDM susceptibility gene. Affected sib pair studies using a simple sequence repeat DNA polymorphism physically linked to the islet amyloid polypeptide and liver glycogen synthase genes showed no evidence for linkage with NIDDM, indicating that they are not major genes contributing to NIDDM susceptibility.

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