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Objective: Frequency domain analysis of heart rate variability (HRV) is used to assess cardiovascular autonomic function. There are no prospective data on the sensitivity of its various components to glycemia or other diabetes-related risk factors compared with conventional tests and with other complications of diabetes.Research Design and Methods: In 1985, possible risk factors of future complications were determined in 115 children with type 1 diabetes. In 1996, the presence of complications (HRV analysis, conventional tests of autonomic function, urinary albumin excretion rate [UAER], and retinopathy) were assessed in 83 of these patients (age 32 +/- 1 years, duration of diabetes 22 +/- 1 years).Results: Poor glycemic control (measured as lifetime glycemic exposure or HbA1c in 1985) was the most important independent predictor of decreases in all measures of absolute power of HRV (total power [TP] and very low frequency, low frequency [LF], and high frequency [HF] power) and square root of the mean square of R-R interval differences but not of changes of normalized measures or ratios (normalized HF and LF LF/HF). Other significant independent predictors of autonomic dysfunction were late age of onset of diabetes, female sex, and high BMI. To examine the sensitivity of the various tests to glycemia, the patients were divided into tertiles based on lifetime glycemic exposure (A1c months). Glycemic exposure in the tertiles averaged 194 +/- 25 A1c months (20 years of HbA1c 0.8% above normal), 556 +/- 19 A1c months(20 years of HbA1c 2.3% above normal), and 963 +/- 30 A1c months (20 years of HbA1c 4% above normal). Tests of complications that were significantly abnormal in patients already in the lowest tertile and were correlated with glycemia were TP and severity of retinopathy. Of conventional tests, only the ratio of length of R-R intervals during expiration to inspiration (E/I ratio) was significantly related to glycemic exposure, but it required high glycemic exposure (20 years of HbA1c 4% above normal) to be abnormal. UAER was significantly increased only in the highest tertile of glycemic exposure.Conclusions: TP and retinopathy score were much more sensitive to antecedent glycemia than conventional tests of autonomic function or UAER and were significantly abnormal in patients exposed to approximately 20 years' duration of an HbA1c 0.8% above normal. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to quantify the excess risk of autoimmune hypothyroidism and hyperthyroidism, Addison disease, celiac disease, and atrophic gastritis in adults with type 1 diabetes (T1D) compared with nondiabetic individuals in Finland., Research Design and Methods: The study included 4,758 individuals with T1D from the Finnish Diabetic Nephropathy (FinnDiane) Study and 12,710 nondiabetic control individuals. The autoimmune diseases (ADs) were identified by linking the data with the Finnish nationwide health registries from 1970 to 2015., Results: The median age of the FinnDiane individuals at the end of follow-up in 2015 was 51.4 (interquartile range 42.6-60.1) years, and the median duration of diabetes was 35.5 (26.5-44.0) years. Of individuals with T1D, 22.8% had at least one additional AD, which included 31.6% of women and 14.9% of men. The odds ratios for hypothyroidism, hyperthyroidism, celiac disease, Addison disease, and atrophic gastritis were 3.43 (95% CI 3.09-3.81), 2.98 (2.27-3.90), 4.64 (3.71-5.81), 24.13 (5.60-104.03), and 5.08 (3.15-8.18), respectively, in the individuals with T1D compared with the control individuals. The corresponding ORs for women compared with men were 2.96 (2.53-3.47), 2.83 (1.87-4.28), 1.52 (1.15-2.02), 2.22 (0.83-5.91), and 1.36 (0.77-2.39), respectively, in individuals with T1D. Late onset of T1D and aging increased the risk of hypothyroidism, whereas young age at onset of T1D increased the risk of celiac disease., Conclusions: This is one of the largest studies quantifying the risk of coexisting AD in adult individuals with T1D in the country with the highest incidence of T1D in the world. The results highlight the importance of continuous screening for other ADs in individuals with T1D., (© 2020 by the American Diabetes Association.)

Both rosiglitazone and metformin increase hepatic insulin sensitivity, but their mechanism of action has not been compared in humans. The objective of this study was to compare the effects of rosiglitazone and metformin treatment on liver fat content, hepatic insulin sensitivity, insulin clearance, and gene expression in adipose tissue and serum adiponectin concentrations in type 2 diabetes. A total of 20 drug-naive patients with type 2 diabetes (age 48 +/- 3 years, fasting plasma glucose 152 +/- 9 mg/dl, BMI 30.6 +/- 0.8 kg/m2) were treated in a double-blind randomized fashion with either 8 mg rosiglitazone or 2 g metformin for 16 weeks. Both drugs similarly decreased HbA1c, insulin, and free fatty acid concentrations. Body weight decreased in the metformin (84 +/- 4 vs. 82 +/- 4 kg, P < 0.05) but not the rosiglitazone group. Liver fat (proton spectroscopy) was decreased with rosiglitazone by 51% (15 +/- 3 vs. 7 +/- 1%, 0 vs. 16 weeks, P = 0.003) but not by metformin (13 +/- 3 to 14 +/- 3%, NS). Rosiglitazone (16 +/- 2 vs. 20 +/- 1 ml.kg(-1).min(-1), P = 0.02) but not metformin increased insulin clearance by 20%. Hepatic insulin sensitivity in the basal state increased similarly in both groups. Insulin-stimulated glucose uptake increased significantly with rosiglitazone but not with metformin. Serum adiponectin concentrations increased by 123% with rosiglitazone but remained unchanged during metformin treatment. The decrease of serum adiponectin concentrations correlated with the decrease in liver fat (r = -0.74, P < 0.001). Rosiglitazone but not metformin significantly increased expression of peroxisome proliferator-activated receptor-gamma, adiponectin, and lipoprotein lipase in adipose tissue. In conclusion, rosiglitazone but not metformin decreases liver fat and increases insulin clearance. The decrease in liver fat by rosiglitazone is associated with an increase in serum adiponectin concentrations. Both agents increase hepatic insulin sensitivity, but only rosiglitazone increases peripheral glucose uptake.

In rodents, food intake and insulin increase ob gene expression and circulating leptin concentrations, but it is unknown whether insulin regulates plasma leptin concentrations in humans. We measured plasma leptin concentrations in 27 normal subjects (16 men, 11 women; age, 24 +/- 1 years; BMI, 22.6 +/- 0.5 kg/m2; body fat, 18 +/- 1%) during a 6-h euglycemic hyperinsulinemic clamp (sequential insulin infusions of 1, 2, and 5 mU.kg-1.min-1 for 2 h each). During these insulin infusions, plasma leptin increased from a basal concentration of 7.4 +/- 1.6 ng/ml by -2 +/- 2, 17 +/- 4, and 50 +/- 6% to 7.2 +/- 1.5 (NS vs. basal), 8.5 +/- 1.7 (P < 0.001), and 10.4 +/- 2.0 ng/ml (P < 0.001), respectively. Of the subjects, eight also participated in a control study where saline was infused for 6 h. In these subjects, plasma leptin increased by 5 +/- 4, 26 +/- 10, and 62 +/- 10% during the insulin infusions, and decreased by 9 +/- 4 (P = 0.07 for change during saline vs. insulin), 13 +/- 4 (P < 0.01), and 17 +/- 4% (P < 0.001) after 2, 4, and 6 h of the saline infusion, respectively. Women had higher plasma leptin concentrations basally and during hyperinsulinemia (P < 0.001) than men, but this difference was entirely accounted for by greater adiposity in women (22 +/- 2 vs. 14 +/- 1%, P < 0.001). These data provide evidence for the insulin regulation of plasma leptin concentrations in humans. This effect requires hours of high insulin concentrations, implying that postprandial satiety is not regulated via changes in plasma leptin concentrations. Insulin may, however, be of importance in the long-term or diurnal regulation of plasma leptin concentrations.