M. James Lenhard

Impact of surgically induced weight loss on cardiovascular autonomic function: one-year follow-up.

Objective: To determine the impact of surgically induced weight loss on cardiovascular autonomic function in subjects with severe obesity and examine whether the effect was comparable for persons with and without diabetes.

Effects of surgically induced weight loss by Roux-en-Y gastric bypass on cardiovascular autonomic nerve function

BACKGROUND Obesity is associated with autonomic imbalance. With respect to cardiovascular autonomic dysfunction, this is characterized by reduced heart rate variability (HRV). Our objective was to determine the effect of surgically induced weight loss on cardiovascular autonomic nerve fiber function in subjects with severe obesity and examine whether an association with reduced insulin resistance exists. The setting was a hospital and private practice in the United States. METHODS A total of 32 morbidly obese patients (body mass index 51 ± 11 kg/m(2)) underwent laparoscopic Roux-en-Y gastric bypass. Measures of HRV (e.g., power spectral analysis, RR variation during deep breathing) were used to evaluate autonomic function before and 6 months after surgery. The homeostasis model assessment of insulin resistance index (HOMA-IR) was used to assess insulin resistance. RESULTS At 6 months after bariatric surgery, the patients had lost 58% excess body mass index with improvement in the HOMA-IR (3.0 ± 1.4 versus 1.1 ± .7; P < .001). Measures of RR variation during deep breathing and total spectral power, low frequency (LF) power (influenced by sympathetic and parasympathetic activity), and high frequency (HF) power (parasympathetic activity) increased with weight loss. The LF/HF ratio was lower (1.5 ± 1.5 versus .9 ± .7, P < .05) with a reduction in weight. Spectral analysis of HRV combined with spectral analysis of respiratory activity generated the respiration frequency area (RFA) and low frequency area. The RFA was increased, and the LFA/RFA ratio was reduced with weight loss. HOMA-IR and HRV did not correlate. CONCLUSION Surgically induced weight loss has a favorable effect on autonomic function, but it does not appear to be directly attributable to reduced insulin resistance.

Hip Strength in Adults With Type 1 Diabetes is Associated With Age at Onset of Diabetes

We investigated the association of age at onset of type 1 diabetes with areal bone mineral density (aBMD), estimates of bone strength, and outer diameter. Using dual-energy X-ray absorptiometry (DXA), aBMD, axial strength (cross-sectional area [CSA]), bending strength (section modulus [SM]), and outer diameter at the narrow neck, intertrochanter, and shaft of the proximal femur were determined for 60 adults. Analysis of covariance (ANCOVA) was used to determine if the DXA-based measures of bone were related to age at onset and if this relationship differed by gender. Age at onset, gender, and the interaction of age at onset by gender were included in the ANCOVA models along with current age, duration, height, lean soft tissue mass, and hemoglobin A1c as covariates. In the adjusted models with CSA, SM, or outer diameter as the dependent variable, age at onset (p<0.01) and gender (p<0.0001) were significant with no interaction. For shaft aBMD, there was a significant age at onset by gender interaction (p=0.0285), where an earlier onset was associated with lower aBMD in the femoral shaft of females but not males. The findings suggest that an earlier onset of type 1 diabetes is associated with lower measures of bone strength and outer diameter.

Insulin therapy for the treatment of type 1 diabetes during pregnancy

Abstract Pregnancies affected by type 1 diabetes (T1D) carry a major risk for poor fetal, neonatal and maternal outcomes. Achieving normoglycemia while minimizing the risk of hypoglycemia is a major goal in the management of T1D as this can greatly reduce the risk of complications. However, maintaining optimal glucose levels is challenging because insulin requirements are not uniform throughout the course of the pregnancy. Over the past decade, there has been significant improvement in the methods for glucose monitoring and insulin administration, accompanied by an increase in the number of treatment options available to pregnant patients with T1D. Through study of the scientific literature and accumulated evidence, we review advances in the management of T1D in pregnancy and offer advice on how to achieve optimal care for the patient.

Zinc Intake and Biochemical Markers of Bone Turnover in Type 1 Diabetes

OBJECTIVE—To examine the relationship between Zn nutritive status and biochemical markers of bone turnover in type 1 diabetes. RESEARCH DESIGN AND METHODS—Serum osteocalcin, urine N-telopeptides, and dietary intake data, obtained by 3-day food records, were assessed for 66 individuals with type 1 diabetes. RESULTS—Zn intake correlated with osteocalcin in the group overall (r = 0.48; P < 0.001) but not with N-telopeptides. Examined by sex, both Zn and osteocalcin correlated for men (r = 0.57; P < 0.001), but the correlation did not reach statistical significance for women (r = 0.34; P = 0.09). A direct-entry linear regression model with osteocalcin as the dependent variable was performed. Duration, sex, A1C, insulin use per kilogram, total calorie intake, and Zn intake were entered as potential independent variables. The model was statistically significant (R2 = 0.32; P < 0.01). Zn intake (P < 0.001), however, was the only independent correlate of osteocalcin. CONCLUSIONS—This study provides evidence of a positive relationship between Zn intake and osteocalcin in type 1 diabetes.

Effect of treatment with losartan on cardiovascular autonomic and large sensory nerve fiber function in individuals with diabetes mellitus: a 1-year randomized, controlled trial.

This study evaluated the effect of losartan, an angiotensin II receptor antagonist, on cardiovascular autonomic function and large sensory nerve fiber function in individuals with diabetes mellitus. In a double-blind placebo-controlled trial, individuals were randomly assigned to treatment with a daily oral dose of 50-mg losartan (n=24) or placebo (n=20) for 12 months. Tests of cardiovascular autonomic function (i.e., RR-variation during deep breathing and the Valsalva maneuver) and of large sensory nerve fiber function (i.e., vibratory thresholds) were measured at baseline and at 12 months. No significant difference at baseline was found for duration of diabetes, glycemic control, blood pressure, or body mass index (BMI) between the two groups. After 12 months, the decline in RR-variation that occurs over time appeared to be less for those taking losartan. There was, however, no statistically significant change in the results for any of the tests of cardiovascular autonomic function or vibratory thresholds between the groups. Multivariate analyses in the losartan study group revealed an independent association of duration of diabetes, change in (reduced) systolic blood pressure (SBP), and improved vibratory thresholds. This association was particularly noted for women. Pharmacologic agents may affect cardiovascular autonomic function by favorable or detrimental changes in the electrophysiology of the heart. The results of this study indicate that, although losartan may have slowed the normal decline in RR-variation, it did not result in any significant improvement in cardiovascular autonomic nerve fiber function. An association of vibratory thresholds and SBP was observed.

A Cross-Sectional Study Comparing Two Quantitative Sensory Testing Devices in Individuals With Diabetes

OBJECTIVE This study was designed to compare circumference discrimination thresholds, as assessed by the Tacticon (Tacticon, Inc., Westtown, PA), a new quantitative sensory testing (QST) device, with vibratory thresholds, an assessment modality of large sensory nerve fibers, in individuals with diabetes. RESEARCH DESIGN AND METHODS In this study, 150 individuals with diabetes were evaluated. Vibratory thresholds and circumference discrimination thresholds, evaluated with the Tacticon, were determined using a two-alternative forced-choice procedure. RESULTS Vibratory thresholds increased with decreasing ability to discriminate differences in circumference (P < 0.001) for those below and above 50 years of age. Agreement between the two QST devices was assessed via the kappa-statistic in both age-groups (i.e., ≤ 50 years old [kappa = 0.67], > 50 years old [κ = 0.55]). In multiple logistic regression, where circumference discrimination thresholds were the dependent variable, age, duration of diabetes, and height were found to be independently associated for those > 50 years old. CONCLUSIONS The Tacticon offers a simple method of assessing the complex function of area discrimination. Our results suggest that the Tacticon can detect neuropathy in the primary care setting. Its cost, portability, and ease of use provide some advantages over existing QST equipment.

Effects of surgically induced weight loss by Roux-en-Y gastric bypass on osteocalcin.

BACKGROUND Osteocalcin (OC), a protein synthesized by osteoblasts, is a marker of bone turnover with undercarboxylated OC (ucOC) being involved in glucose homeostasis. Although laparoscopic Roux-en-Y gastric bypass (LRYGB)-induced weight loss likely alters bone turnover, data on markers of bone turnover remain less clear. The aim of this study was to examine the effect of surgically induced weight loss on OC and ucOC. METHODS A total of 32 individuals with a body mass index 50.2±10.2 kg/m(2) underwent LRYGB. Osteocalcin, ucOC, other blood analytes (e.g., vitamin D, leptin, total and high-molecular-weight adiponectin), and homeostasis model assessment for insulin resistance were measured before and after weight loss. The effect of an acute nutrient load on OC parameters after a mixed meal tolerance test also was assessed. RESULTS Six months after surgery, there was an increase in OC (17.8±7.4 [mean±SD] [baseline] versus 31.5±9.8 ng/mL [follow-up]; P<.001) and ucOC (7.3±6.2 versus 18.5±8.9 ng/mL; P<.001). Although adiponectin increased, only the magnitude of change in OC and leptin was correlated (r =-.43; P = .017). After weight loss, an acute nutrient load reduced OC (31.5±9.8 [0-hour] versus 29.6±8.2 [2-hour] ng/mL; P = .024), whereas ucOC was higher (18.8±9.3 [0-hour] versus 21.1±8.6 [2-hour] ng/mL; P< .001). CONCLUSION Surgically induced weight loss was associated with increases in OC and ucOC. Underlying mechanisms are unclear, but change in OC may be related to change in leptin. After a nutrient load, the increase in ucOC suggests a potential role as a short-term compensatory regulator of glucose homeostasis.

Autonomic nerve fiber function and bone mineral density in individuals with type 1 diabetes: a cross-sectional study.

AIMS Experimental models support a role for the sympathetic nervous system in bone metabolism. Beta-adrenoreceptors have been demonstrated on osteoblast-like cells. Beta-blocker use is associated with higher bone mineral density (BMD) in some epidemiologic studies. The aim of this study was to determine if measures of the autonomic nervous system (ANS) were associated with reduced BMD in type 1 diabetes. METHODS We studied 66 individuals with type 1 diabetes. Dual-energy X-ray absorptiometry was used to measure BMD and bone mineral content (BMC). Measures of heart rate variability (HRV) (e.g., power spectral analysis, mean circular resultant) and circulating norepinephrine levels were used to evaluate autonomic function. RESULTS BMD/BMC were examined by gender for individuals with a normal versus elevated low-frequency (LF) band (expressed in normalized units). No significant differences in BMD/BMC were shown for individuals with an elevated LF band. Direct-entry linear regression models with BMD/BMC as the dependent variable were performed. Duration, gender, BMI, HbA(1c), insulin dose/kg, activity energy expenditure, and measures of HRV were entered as potential independent variables. No measures of HRV, or norepinephrine, were independently associated with BMD/BMC. CONCLUSIONS The ANS, as assessed by measures of HRV, does not appear to impact BMD/BMC in type 1 diabetes.

Pre-heparin lipoprotein lipase mass as a potential mediator in the association between adiponectin and HDL-cholesterol in type 2 diabetes

Highlights • We examined pre-heparin LPL mass in type 2 diabetes mellitus (T2DM).• Association of adiponectin, pre-heparin LPL mass, and HDL-C was examined in T2DM.• Pre-heparin LPL mass may mediate the adiponectin and HDL-C association in T2DM.