The Prediabetic Period: Review of Clinical Aspects

Hyperglycemia that does not satisfy the diagnostic criteria for diabetes mellitus (DM) is generally called prediabetes (preDM). The global prevalence of preDM has been increasing progressively in the past few decades, and it has been established that preDM status is a strong risk factor for DM and cardiovascular disease. Currently, preDM status is classified into two subtypes: impaired fasting glucose and impaired glucose tolerance. Currently, preDM is not regarded as an independent clinical entity, but only as a risk factor for others. In this article, we review various clinical aspects of preDM in terms of the working definition, changes in criteria over the years, epidemiology, and pathophysiological characteristics, and its clinical significance in current medicine

Type 2 Diabetes and the Risk of Renal Cell Cancer in Women

Objective: Type 2 diabetes is associated with increased risks of several types of cancer; however, its relationship to renal cell cancer remains unclear. Research Design and Methods: A total of 118,177 women aged 30 to 55 years at baseline (1976) were followed up through 2008 in the Nurses’ Health Study. Self-reports of physician-diagnosed diabetes were collected at baseline and updated biennially. Hazard ratios (HRs) were calculated using Cox proportional hazards models with adjustment for age, BMI, hypertension, smoking, and parity. Results: During 32 years of follow-up (3,531,170 person-years), 16,819 cases of type 2 diabetes and 330 cases of pathology-confirmed incident renal cell cancer were documented. After multivariate adjustment, type 2 diabetes was significantly associated with an increased risk of renal cell cancer (HR 1.60 [95% CI 1.19–2.17]). These associations were consistent across different strata of BMI, smoking, and hypertension ($P_{interaction} \geq 0.32$). The risk of renal cell cancer increased with an increasing number of comorbidities, including obesity, hypertension, and type 2 diabetes ($P_{trend} < 0.001$). When compared with women without any comorbidity, women who had all three conditions had a HR of 4.13 (2.76–6.18) for renal cell cancer. Conclusions: Type 2 diabetes is independently associated with an increased risk of renal cell cancer in women. In addition, comorbidity of obesity, hypertension, and type 2 diabetes substantially elevates the risk of renal cell cancer

Site-Specific GlcNAcylation of Human Erythrocyte Proteins: Potential Biomarker(s) for Diabetes

OBJECTIVE—O-linked N-acetylglucosamine (O-GlcNAc) is upregulated in diabetic tissues and plays a role in insulin resistance and glucose toxicity. Here, we investigated the extent of GlcNAcylation on human erythrocyte proteins and compared site-specific GlcNAcylation on erythrocyte proteins from diabetic and normal individuals

Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals

AIMS/HYPOTHESIS: We conducted genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) analyses to identify and characterise risk loci for type 2 diabetes in Mexican-Americans from Starr County, TX, USA. METHOD: Using 1.8 million directly interrogated and imputed genotypes in 837 unrelated type 2 diabetes cases and 436 normoglycaemic controls, we conducted Armitage trend tests. To improve power in this population with high disease rates, we also performed ordinal regression including an intermediate class with impaired fasting glucose and/or glucose tolerance. These analyses were followed by meta-analysis with a study of 967 type 2 diabetes cases and 343 normoglycaemic controls from Mexico City, Mexico. RESULT: The top signals (unadjusted p value <1×10(−5)) included 49 single nucleotide polymorphisms (SNPs) in eight gene regions (PER3, PARD3B, EPHA4, TOMM7, PTPRD, HNT [also known as RREB1], LOC729993 and IL34) and six intergenic regions. Among these was a missense polymorphism (rs10462020; Gly639Val) in the clock gene PER3, a system recently implicated in diabetes. We also report a second signal (minimum p value 1.52× 10(−6)) within PTPRD, independent of the previously implicated SNP, in a population of Han Chinese. Top meta-analysis signals included known regions HNF1A and KCNQ1. Annotation of top association signals in both studies revealed a marked excess of trans-acting eQTL in both adipose and muscle tissues. CONCLUSIONS/INTERPRETATION: In the largest study of type 2 diabetes in Mexican populations to date, we identified modest associations of novel and previously reported SNPs. In addition, in our top signals we report significant excess of SNPs that predict transcript levels in muscle and adipose tissues

Diagnostic criteria for diabetes revisited: making use of combined criteria

BACKGROUND: Existing cut-offs for fasting plasma glucose (FPG) and post-load glucose (2hPG) criteria are not equivalent in the diagnosis of diabetes and glucose intolerance. Adjusting cut-offs of single measurements have not helped so we undertook this project to see if they could be complementary. METHODS: We performed oral glucose tolerance tests and mean levels of hemoglobin A1c (HbA1c) measurements on 43 patients referred to a diabetes clinic for possible diabetes. Results of single and combined use of the FPG and 2hPG criteria were evaluated against the levels of HbA1c and results re-interpreted in the light of existing reports in the literature. RESULTS: Our results confirm that the FPG and the 2hPG, being specific and sensitive respectively for the presence of glucose intolerance or diabetes, are not equivalent. They are shown to be indeed complementary and a re-definition of diagnostic criteria based on their combined use is proposed. CONCLUSIONS: We conclude that altering single measurement cut-offs for the diagnosis of diabetes and altered glucose tolerance will not result in better outcomes. We present the case for a combined criteria in the diagnosis and definition of diabetes with a FPG≥7 mmol/L AND 2-hour glucose ≥7.8 mmol/L being used to define diabetes while a FPG<7 mmol/L AND 2-hour glucose <7.8 mmol/L being used to define normality. Discordant values will define impaired glucose tolerance (IGT). This proposal requires prospective evaluation in a large cohort