The effect of surgical weight loss on diabetes complications in individuals with class II/III obesity.

AIMS/HYPOTHESIS: The aim of this study was to determine the effect of bariatric surgery on diabetes complications in individuals with class II/III obesity (BMI > 35 kg/m2). METHODS: We performed a prospective cohort study of participants with obesity who underwent bariatric surgery. At baseline and 2 years following surgery, participants underwent metabolic phenotyping and diabetes complication assessments. The primary outcomes for peripheral neuropathy (PN) were a change in intra-epidermal nerve fibre density (IENFD, units = fibres/mm) at the distal leg and proximal thigh, the primary outcome for cardiovascular autonomic neuropathy (CAN) was a change in the expiration/inspiration (E/I) ratio, and the primary outcome for retinopathy was a change in the mean deviation on frequency doubling technology testing. RESULTS: Among 127 baseline participants, 79 completed in-person follow-up (age 46.0 ± 11.3 years [mean ± SD], 73.4% female). Participants lost a mean of 31.0 kg (SD 18.4), and all metabolic risk factors improved except for BP and total cholesterol. Following bariatric surgery, one of the primary PN outcomes improved (IENFD proximal thigh, +3.4 ± 7.8, p<0.01), and CAN (E/I ratio -0.01 ± 0.1, p=0.89) and retinopathy (deviation -0.2 ± 3.0, p=0.52) were stable. Linear regression revealed that a greater reduction in fasting glucose was associated with improvements in retinopathy (mean deviation point estimate -0.7, 95% CI -1.3, -0.1). CONCLUSIONS/INTERPRETATION: Bariatric surgery may be an effective approach to reverse PN in individuals with obesity. The observed stability of CAN and retinopathy may be an improvement compared with the natural progression of these conditions; however, controlled trials are needed.

Dietary weight loss in people with severe obesity stabilizes neuropathy and improves symptomatology.

OBJECTIVE: The aim of this study was to determine the effect of dietary weight loss on neuropathy outcomes in people with severe obesity. METHODS: A prospective cohort study of participants attending a medical weight-management program was followed. Weight loss was achieved with meal replacement of 800 kcal/d for 12 weeks and then transitioning to 1,200 to 1,500 kcal/d. The coprimary outcomes were changes in intraepidermal nerve fiber density (IENFD) at the distal leg and proximal thigh. Secondary outcomes included nerve conduction studies, Michigan Neuropathy Screening Instrument questionnaire and exam, Quality of Life in Neurological Disorders, and quantitative sensory testing. RESULTS: Among 131 baseline participants, 72 (mean [SD] age: 50.1 [10.5] years, 51.4% female) completed 2 years of follow-up. Participants lost 12.4 (11.8) kg. All metabolic syndrome components improved with the exception of blood pressure. IENFD in the distal leg (0.4 [3.3], p = 0.29), and proximal thigh (0.3 [6.3], p = 0.74) did not significantly change. Improvements were observed on the Michigan Neuropathy Screening Instrument questionnaire, two Quality of Life in Neurological Disorders subdomains, and quantitative sensory testing cold threshold. CONCLUSIONS: Dietary weight loss was associated with improvements in all metabolic parameters except blood pressure, and both IENFD outcomes remained stable after 2 years. Given that natural history studies reveal decreases in IENFD over time, dietary weight loss may halt this progression, but randomized controlled trials are needed.

Central Obesity is Associated With Neuropathy in the Severely Obese.

OBJECTIVE: To determine the prevalence of neuropathy stratified by glycemic status and the association between extensive anthropometric measurements and neuropathy. PATIENTS AND METHODS: We performed a cross-sectional, observational study in obese individuals, before surgery, with body mass index (BMI) greater than 35 kg/m2. Lean controls were recruited from a research website. Neuropathy was defined by the Toronto consensus definition of probable neuropathy. We compared nine anthropometric measurements between obese participants with and without neuropathy. We used multivariable logistic regression to explore associations between these measures, and other metabolic risk factors, and neuropathy. RESULTS: We recruited 138 obese individuals and 46 lean controls. The mean age (SD) was 45.1 (11.3) years in the obese population (76.1% female, n=105) and 43.8 (12.1) years in the lean controls (82.2% female, n=37). The prevalence of neuropathy was 2.2% (n=1) in lean controls, 12.1% (n=4) in obese participants with normoglycemia, 7.1% (n=4) in obese participants with pre-diabetes, and 40.8% (n=20) in obese participants with diabetes (p≤.01). Waist circumference was the only anthropometric measure that was larger in those with neuropathy (139.3 cm vs 129.1 cm, p=.01). Hip-thigh (71.1 cm vs 76.6 cm, p<.01) and mid-thigh (62.2 cm vs 66.3 cm, p=.03) circumferences were smaller in those with neuropathy. The body mass index was comparable between patients who were obese with and without neuropathy (p=.86). Waist circumference (odds ratio [OR], 1.39; 95% CI, 1.10 to 1.75), systolic blood pressure (OR, 2.89; 95% CI, 1.49 to 5.61), and triglycerides (OR, 1.31; 95% CI, 1.00 to 1.70) were significantly associated with neuropathy. CONCLUSION: Normoglycemic obese patients have a high prevalence of neuropathy indicating that obesity alone may be sufficient to cause neuropathy. Waist circumference, but not general obesity, is significantly associated with neuropathy.

The Prevalence and Determinants of Cognitive Deficits and Traditional Diabetic Complications in the Severely Obese.

OBJECTIVE: To determine the prevalence of cognitive deficits and traditional diabetic complications and the association between metabolic factors and these outcomes. RESEARCH DESIGN AND METHODS: We performed a cross-sectional study in severely obese individuals before bariatric surgery. Lean control subjects were recruited from a research website. Cognitive deficits were defined by the National Institutes of Health (NIH) Toolbox (<5th percentile for lean control subjects). Cardiovascular autonomic neuropathy (CAN) was defined by an expiration-to-inspiration (E-to-I) ratio of <5th percentile for lean control subjects. Retinopathy was based on retinal photographs and nephropathy on the estimated glomerular filtration rate (<60 mg/dL) and/or the albumin-to-creatinine ratio (ACR) (≥30 mg/g). NIH Toolbox, E-to-I ratio, mean deviation on frequency doubling technology testing, and ACR were used as sensitive measures of these outcomes. We used multivariable linear regression to explore associations between metabolic factors and these outcomes. RESULTS: We recruited 138 severely obese individuals and 46 lean control subjects. The prevalence of cognitive deficits, CAN, retinopathy, and nephropathy were 6.5%, 4.4%, 0%, and 6.5% in lean control subjects; 22.2%, 18.2%, 0%, and 6.1% in obese participants with normoglycemia; 17.7%, 21.4%, 1.9%, and 17.9% in obese participants with prediabetes; and 25.6%, 31.9%, 6.1%, and 16.3% in obese participants with diabetes. Waist circumference was significantly associated with cognitive function (-1.48; 95% CI -2.38, -0.57) and E-to-I ratio (-0.007; 95% CI -0.012, -0.002). Prediabetes was significantly associated with retinal function (-1.78; 95% CI -3.56, -0.002). CONCLUSIONS: Obesity alone is likely sufficient to cause cognitive deficits but not retinopathy or nephropathy. Central obesity is the key metabolic risk factor.

Better diagnostic accuracy of neuropathy in obesity: A new challenge for neurologists.

OBJECTIVE: To determine the comparative diagnostic characteristics of neuropathy measures in an obese population. METHODS: We recruited obese participants from the University of Michigan's Weight Management Program. Receiver operative characteristic analysis determined the area under the curve (AUC) of neuropathy measures for distal symmetric polyneuropathy (DSP), small fiber neuropathy (SFN), and cardiovascular autonomic neuropathy (CAN). The best test combinations were determined using stepwise and Score subset selection models. RESULTS: We enrolled 120 obese participants. For DSP, seven of 42 neuropathy measures (Utah Early Neuropathy Score (UENS, N = 62), Michigan Neuropathy Screening Instrument (MNSI) reduced combined index, MNSI examination, nerve fiber density (NFD) leg, tibial F response, MNSI questionnaire, peroneal distal motor latency) had AUCs ≥ 0.75. Three of 19 small fiber nerve measures for SFN (UENS, NFD leg, Sudoscan feet (N = 70)) and zero of 16 CAN measures had AUCs ≥ 0.75. Combinations of tests performed better than individual tests with AUCs of 0.82 for DSP (two parameters) and 0.84 for SFN (three parameters). CONCLUSIONS: Many neuropathy measures demonstrate good test performance for DSP in obese participants. Select few small fiber nerve measures performed well for SFN, and none for CAN. SIGNIFICANCE: Specific combinations of tests should be used for research studies to maximize diagnostic performance in obese cohorts.

Association Between Metabolic Syndrome Components and Polyneuropathy in an Obese Population.

IMPORTANCE: Past studies have shown an association between metabolic syndrome and polyneuropathy, but the precise components that drive this association remain unclear. OBJECTIVES: To determine the prevalence of polyneuropathy stratified by glycemic status in well-characterized obese and lean participants and investigate the association of specific components of metabolic syndrome with polyneuropathy. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional, observational study from November 1, 2010, to December 31, 2014, in obese participants (body mass index [calculated as weight in kilograms divided by height in meters squared] of 35 or more with no comorbid conditions or 32 or more with at least 1 comorbid condition) from a weight management program and lean controls from a research website. The prevalence of neuropathy, stratified by glycemic status, was determined, and a Mantel-Haenszel χ2 test was used to investigate for a trend. Logistic regression was used to model the primary outcome of polyneuropathy as a function of the components of metabolic syndrome after adjusting for demographic factors. Participants also completed quantitative sudomotor axon reflex testing, quantitative sensory testing, the neuropathy-specific Quality of Life in Neurological Disorders instrument, and the short-form McGill Pain Questionnaire. EXPOSURES: Components of metabolic syndrome (as defined by the National Cholesterol Education Program Adult Treatment Panel III), including glycemic status (as defined by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus). MAIN OUTCOMES AND MEASURES: Toronto consensus definition of probable polyneuropathy. Secondary outcomes included intraepidermal nerve fiber density and nerve conduction study parameters. RESULTS: We enrolled 102 obese participants (mean [SD] age, 52.9 [10.2] years; 48 men and 54 women; 45 with normoglycemia [44.1%], 31 with prediabetes [30.4%], and 26 with type 2 diabetes [25.5%]) and 53 lean controls (mean [SD] age, 48.5 [9.9] years; 16 men and 37 women). The prevalence of polyneuropathy was 3.8% in lean controls (n = 2), 11.1% in the obese participants with normoglycemia (n = 5), 29% in the obese participants with prediabetes (n = 9), and 34.6% in the obese participants with diabetes (n = 9) (P < .01 for trend). Age (odds ratio, 1.09; 95% CI, 1.02-1.16), diabetes (odds ratio, 4.90; 95% CI, 1.06-22.63), and waist circumference (odds ratio, 1.24; 95% CI, 1.00-1.55) were significantly associated with neuropathy in multivariable models. Prediabetes (odds ratio, 3.82; 95% CI, 0.95-15.41) was not significantly associated with neuropathy. CONCLUSIONS AND RELEVANCE: The prevalence of polyneuropathy is high in obese individuals, even those with normoglycemia. Diabetes, prediabetes, and obesity are the likely metabolic drivers of this neuropathy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02689661.