OBJECTIVE

To test whether diabetic polyneuropathies (DPNs), retinopathy, or nephropathy is more prevalent in subjects with impaired glycemia (IG) (abnormality of impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA1c [IA1C]) than in healthy subjects (non-IG).

RESEARCH DESIGN AND METHODS

Matched IG and non-IG volunteers were randomly identified from population-based diagnostic and laboratory registries, restudied, and reclassified as non-IG (n = 150), IG (n = 174), or new diabetes (n = 218).

RESULTS

Frequency (%) of DPN in non-IG, IG, and new diabetes was 3 (2.0%), 3 (1.7%), and 17 (7.8%) narrowly defined (no other cause for polyneuropathy) and 19 (12.7%), 22 (12.6%), and 38 (17.4%) broadly defined. Mean and frequency distribution of composite scores of nerve conduction and quantitative sensation tests were not significantly different between IG and non-IG but were worse in new diabetes. Frequency of retinopathy and nephropathy was significantly increased only in new diabetes. In secondary analysis, small but significant increases in retinopathy and nephropathy were found in IGT, IFG, and IGT combined groups.

CONCLUSIONS

In population studies of Olmsted County, Minnesota, inhabitants, prevalence of typical DPN, retinopathy, and nephropathy was significantly increased only in subjects with new diabetes—not in subjects with IG as defined by American Diabetes Association (ADA) criteria of abnormality of IFG, IGT, or IA1C. For atypical DPN, such an increase was not observed even in subjects with new diabetes. In medical practice, explanations other than IG should be sought for patients with atypical DPN (chronic idiopathic axonal polyneuropathy) who have IG.

OBJECTIVE

Unlike visceral adipose tissue (VAT), the association between subcutaneous adipose tissue (SAT) and obesity-related morbidity is controversial. In patients with type 2 diabetes, we assessed whether this variability can be explained by a putative favorable, distinct association between abdominal superficial SAT (SSAT) (absolute amount or its proportion) and cardiometabolic parameters.

RESEARCH DESIGN AND METHODS

We performed abdominal magnetic resonance imaging (MRI) in 73 patients with diabetes (mean age 58 years, 83% were men) and cross-sectionally analyzed fat distribution at S1-L5, L5-L4, and L3-L2 levels. Patients completed food frequency questionnaires, and subgroups had 24-h ambulatory blood pressure monitoring and 24-h ambulatory electrocardiography.

RESULTS

Women had higher %SSAT (37 vs. 23% in men; P < 0.001) despite a similar mean waist circumference. Fasting plasma glucose (P = 0.046) and HbA1c (P = 0.006) were both lower with increased tertile of absolute SSAT. In regression models adjusted for age, waist circumference, and classes of medical treatments used in this patient population, increased %SSAT was significantly associated with decreased HbA1c (β = −0.317; P = 0.013), decreased daytime ambulatory blood pressure (β = −0.426; P = 0.008), and increased HDL cholesterol (β = 0.257; P = 0.042). In contrast, increased percent of deep SAT (DSAT) was associated with increased HbA1c (β = 0.266; P = 0.040) and poorer heart rate variability parameters (P = 0.030). Although total fat and energy intake were not correlated with fat tissue distribution, increased intake of trans fat tended to be associated with total SAT (r = 0.228; P = 0.05) and DSAT (r = 0.20; P = 0.093), but not with SSAT.

CONCLUSIONS

Abdominal SAT is composed of two subdepots that associate differently with cardiometabolic parameters. Higher absolute and relative distribution of fat in abdominal SSAT may signify beneficial cardiometabolic effects in patients with type 2 diabetes.

OBJECTIVE

In young-onset diabetes, insulin therapy status is a rough marker of diabetes type. We describe the mortality experience of a low-income, predominantly minority population with diabetes diagnosed before age 30 years, stratified by insulin therapy.

RESEARCH DESIGN AND METHODS

A total of 1,098 adults aged 40–79 years (median 49) diagnosed with diabetes before age 30 years and 49,914 without diabetes were recruited from community health centers. Individuals with diabetes were categorized by insulin therapy at baseline: group A, insulin therapy only; group B, insulin therapy and an oral hypoglycemic agent; and group C, no insulin therapy. Cox models were used to compute hazard ratios (HRs) and 95% CI for cause-specific mortality based on both underlying and contributing causes of death from death certificates.

RESULTS

During follow-up (mean 3.9 years), 15.0, 12.5, and 7.3% of groups A, B, and C, respectively, and 4.6% without diabetes died. Compared with individuals without diabetes, HRs (CI) for all-cause mortality were 4.3 (3.4–5.6), 4.2 (2.8–6.3), and 2.0 (1.4–2.8) in groups A, B, and C, respectively. The leading cause of death was renal failure (end-stage renal disease [ESRD]) in group A, ESRD and coronary artery disease (CAD) in group B, and CAD in group C and individuals without diabetes. HRs for these conditions were at least twice as high as the HRs for all-cause mortality, reaching 17.3 (10.2–29.3), 17.9 (8.3–38.7), and 5.1 (2.3–11.7) in groups A, B, and C, respectively, for ESRD.

CONCLUSIONS

Excess mortality persists among people with young-onset diabetes of long duration, with ESRD and CAD as the leading contributors to mortality.

OBJECTIVE

Biochemical heterogeneity governs functional disparities among lipoproteins. We examined charge-defined VLDL subfractions in metabolic syndrome (MetS) to determine whether their increased electronegativity is associated with increased cytotoxicity and whether high concentrations of highly electronegative subfractions render VLDL harmful to the vascular endothelium.

RESEARCH DESIGN AND METHODS

Plasma VLDL of normal individuals (control subjects) (n = 13) and of those with MetS (n = 13) was resolved into subfractions with increasing negative charge (V1–V5) by anion-exchange chromatography. Human aortic endothelial cells were treated with V1–V5 or unfractionated VLDL.

RESULTS

Compared with the control subjects, individuals with MetS had a significantly higher percentage of V5 VLDL (V5/VLDL%) (34 ± 20 vs. 39 ± 11%, respectively; P < 0.05) and plasma V5 concentration ([V5]) (5.5 ± 4.4 vs. 15.2 ± 8.5 mg/dL, respectively; P < 0.001). Apolipoprotein (apo)B100 levels decreased and apoC levels increased from V1 to V5, indicating that V5 is apoC-rich VLDL. Regression analyses of all 26 individuals showed that [V5] was positively correlated with total cholesterol (P = 0.016), triglyceride (P < 0.000001), and V5/VLDL% (P = 0.002). Fasting plasma glucose, but not waist circumference, exhibited a positive trend (P = 0.058); plasma HDL cholesterol exhibited a weak inverse trend (P = 0.138). V5 (10 μg/mL) induced apoptosis in ~50% of endothelial cells in 24 h. V5 was the most rapidly (<15 min) internalized subfraction and induced the production of reactive oxygen species (ROS) in endothelial cells after 20 min. Unfractionated MetS VLDL, but not control VLDL, also induced ROS production and endothelial cell apoptosis.

CONCLUSIONS

In populations with increased risk of diabetes, the vascular endothelium is constantly exposed to VLDL that contains a high proportion of V5. The potential impact of V5-rich VLDL warrants further investigation.

OBJECTIVE

To identify the characteristics associated with glycemic response to newly initiated insulin therapy.

RESEARCH DESIGN AND METHODS

We identified 1,139 type 2 diabetic patients who initiated insulin therapy between 1 January 2009 and 30 June 2010. Outcomes of interest were the proportion of patients achieving A1C <7% and mean change in A1C within 3–9 months.

RESULTS

Mean A1C at insulin initiation was 8.2 vs. 9.2% among those who did and did not attain A1C <7% (P < 0.001). Within a mean of 5 months, 464 (40.7%) patients attained A1C <7%. In multivariable analyses controlling for insulin regimen, dose, and oral agent use, preinsulin A1C was responsible for nearly all the explained variance in A1C change. Each one percentage point of preinsulin A1C reduced the probability of attaining <7% by 26% (odds ratio 0.74 [95% CI 0.68–0.80]).

CONCLUSIONS

Insulin initiation at lower levels of A1C improves goal attainment and independently increases glycemic response.

OBJECTIVE

To define a panel of novel protein biomarkers of renal disease.

RESEARCH DESIGN AND METHODS

Adults with type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study who were initially free of renal complications (n = 465) were followed for development of micro- or macroalbuminuria (MA) and early renal function decline (ERFD, annual decline in estimated glomerular filtration rate of ≥3.3%). The label-free proteomic discovery phase was conducted in 13 patients who progressed to MA by the 6-year visit and 11 control subjects, and four proteins (Tamm-Horsfall glycoprotein, α-1 acid glycoprotein, clusterin, and progranulin) identified in the discovery phase were measured by enzyme-linked immunosorbent assay in 74 subjects: group A, normal renal function (n = 35); group B, ERFD without MA (n = 15); group C, MA without ERFD (n = 16); and group D, both ERFD and MA (n = 8).

RESULTS

In the label-free analysis, a model of progression to MA was built using 252 peptides, yielding an area under the curve (AUC) of 84.7 ± 5.3%. In the validation study, ordinal logistic regression was used to predict development of ERFD, MA, or both. A panel including Tamm-Horsfall glycoprotein (odds ratio 2.9, 95% CI 1.3–6.2, P = 0.008), progranulin (1.9, 0.8–4.5, P = 0.16), clusterin (0.6, 0.3–1.1, P = 0.09), and α-1 acid glycoprotein (1.6, 0.7–3.7, P = 0.27) improved the AUC from 0.841 to 0.889.

CONCLUSIONS

A panel of four novel protein biomarkers predicted early renal damage in type 1 diabetes. These findings require further validation in other populations for prediction of renal complications and treatment monitoring.

OBJECTIVE

The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recently recommended new criteria for diagnosing gestational diabetes mellitus (GDM). This study was undertaken to determine whether adopting the IADPSG criteria would be cost-effective, compared with the current standard of care.

RESEARCH DESIGN AND METHODS

We developed a decision analysis model comparing the cost-utility of three strategies to identify GDM: 1) no screening, 2) current screening practice (1-h 50-g glucose challenge test between 24 and 28 weeks followed by 3-h 100-g glucose tolerance test when indicated), or 3) screening practice proposed by the IADPSG. Assumptions included that 1) women diagnosed with GDM received additional prenatal monitoring, mitigating the risks of preeclampsia, shoulder dystocia, and birth injury; and 2) GDM women had opportunity for intensive postdelivery counseling and behavior modification to reduce future diabetes risks. The primary outcome measure was the incremental cost-effectiveness ratio (ICER).

RESULTS

Our model demonstrates that the IADPSG recommendations are cost-effective only when postdelivery care reduces diabetes incidence. For every 100,000 women screened, 6,178 quality-adjusted life-years (QALYs) are gained, at a cost of $125,633,826. The ICER for the IADPSG strategy compared with the current standard was $20,336 per QALY gained. When postdelivery care was not accomplished, the IADPSG strategy was no longer cost-effective. These results were robust in sensitivity analyses.

CONCLUSIONS

The IADPSG recommendation for glucose screening in pregnancy is cost-effective. The model is most sensitive to the likelihood of preventing future diabetes in patients identified with GDM using postdelivery counseling and intervention.