Patterns of Weight Loss Medication Utilization and Outcomes Following Bariatric Surgery.

BACKGROUND: Bariatric surgery is the most effective treatment for obesity; however, some patients experience significant weight regain. Weight loss medications (WLM) are being increasingly used in surgery patients with limited evidence. We examine weight loss outcomes in patients using WLM after bariatric surgery. METHODS: In a retrospective study, 197 bariatric surgery patients who started WLM between 2016 and 2019 at a single center were analyzed. Patients were categorized into 3 groups based on outcomes of the initial surgery: (1) Weight regainers (WR) = achieved goal weight loss after surgery (15% total body weight loss (TBWL) for sleeve gastrectomy (SG) and 25% TBWL for Roux-en-Y gastric bypass (RYGB)) with subsequent regain of > 20% of weight lost; (2) Adequate weight loss (AWL) = achieved goal weight loss without > 20% weight regain; (3) Non-responders (NR) = never achieved goal weight loss. Weight loss and medication use patterns were analyzed. RESULTS: Among the three categories, there was no significant difference in duration of medical therapy or %TBWL with medications. RYGB patients lost more weight than SG patients using WLM (p = 0.03). Of the medications used, patients treated with phentermine + topiramate had the highest likelihood of achieving 5%, 10%, and 15% weight loss. Compared to other 2 groups, AWL group initiated WLM earlier and experienced more weight loss when compared to their pre-operative weight or post-operative nadir. CONCLUSIONS: RYGB patients respond better to WLM than SG patients. Those who had started WLM before regaining weight (AWL) experienced greater overall weight loss, suggesting that proactive medical therapy at the time of weight plateau can help with greater total weight loss. Phentermine + topiramate is the most effective WLM in post-bariatric surgery patients.

Type 2 diabetes in children and adolescents on atypical antipsychotics.

Youth receiving treatment with antipsychotics are particularly susceptible to weight gain, type 2 diabetes (T2D), and associated metabolic disorders, which is directly associated with excess morbidity and mortality in this vulnerable population. The risk of T2D is 2- to 3-fold that of the general population, starts early in the course of treatment, and reflects the effects of weight gain in conjunction with direct effects of antipsychotics on the hypothalamus, pancreatic beta cells, and insulin-sensitive peripheral tissues. Close monitoring with early intervention through lifestyle intervention, switching away from antipsychotics with deleterious metabolic effects, and adjunctive treatment with metformin are modalities available to mitigate weight gain and improve cardiometabolic health in these patients. Despite rapidly advancing knowledge in the field, patient's access to metabolic screening and quality care remains limited. Efforts must be made to broaden reach of early cardiometabolic intervention among these patients in order to avert serious cardiovascular disease burden in the future.

Weight-loss programs in convenient care clinics: a prospective cohort study.

PURPOSE: Assess whether a convenient care clinic (CCC) medical weight-loss program can promote weight loss. DESIGN: Prospective cohort study with follow-up at 10 weeks. SETTING: A CCC (Lindora Health Clinic) weight-loss program (Lean for Life) based in a retail pharmacy (Rite Aid Pharmacy) in Costa Mesa, California. SUBJECTS: The first 100 people to purchase the weight-loss program. INTERVENTION: A 10-week, $465 medical weight-loss program with individual counseling sessions; a hypocaloric diet of 900 to 1200 kcal/day (25%-30% carbohydrates, 40% protein, 25% fat); and adjunctive pharmacologic treatment, if necessary. MEASURES: We collected data on age, height, weight, visits per week, medication use, comorbid conditions, and weight change. ANALYSIS: Data were analyzed based on length of enrollment and mean percent weight loss. Statistical tests used were t-test and Spearman rank correlation test. RESULTS: Eighty-six subjects had valid data entries for weight change over the 10-week period. Average age was 51.6 years; mean starting body mass index was 30.3. Thirty patients participated for 0 to 4 weeks, 30 for 4 to 9 weeks, and 26 for 10 weeks. Mean percent weight changes for the 0 to 4, 5 to 9, and 10-week groups were -1.6, -6.0, and -8.1, respectively. Forty-five (45%) of the patients achieved medically significant weight loss (> or =5%). CONCLUSION: The study shows that a medical weight-loss program offered at a CCC in a retail pharmacy can produce medically significant weight loss of > or =5%. Further research of collaborations between the retail and medical weight-loss industries is warranted. Study design limitations included selection bias and confounding variables other than the weight-loss program.

Metabolic syndrome with the atypical antipsychotics.

PURPOSE OF REVIEW: Metabolic syndrome and cardiovascular diseases are important causes of morbidity and mortality among patients with severe mental illnesses. Atypical or second-generation antipsychotics (SGAs) are associated with obesity and other components of metabolic syndrome, particularly abnormal glucose and lipid metabolism. This review aims to provide a summary of recent evidence on metabolic risks associated with SGAs, current recommendations for metabolic monitoring, and efficacy of treatment options currently available. RECENT FINDINGS: Studies have identified younger, antipsychotic-naive patients with first-episode psychosis as a population vulnerable to adverse metabolic effects from SGAs. These patients gained more weight and developed evident lipid and glucose abnormalities as soon as 8-12 weeks after treatment initiation. Findings are more striking among children and adolescents. The differential effects of various SGAs are well described, with clozapine and olanzapine associated with the highest metabolic risk. In addition to behavioral therapy, emerging data suggest that pharmacological therapy, most notably metformin, is efficacious in the treatment and possibly prevention of SGA-associated metabolic derangements. SUMMARY: More data have become available on the burden from metabolic complications associated with SGAs. New and effective treatment options are required in the near future to improve cardiovascular health in this susceptible population.

Treating diabetes and prediabetes by focusing on obesity management.

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In obesity, the adipose cell releases nonesterified free fatty acids, hormones, adipocytokines, and other substances that are involved in insulin resistance. Under normal conditions, the pancreatic islet beta cells increase production of insulin sufficiently to maintain normal blood glucose concentrations despite insulin resistance. However, in genetically predisposed patients, the beta cells eventually become dysfunctional and T2DM develops. The development of T2DM can be delayed or sometimes prevented in individuals with obesity who are able to lose weight. Weight loss can be achieved medically with behavioral therapies that combine diet and exercise treatment or with behavioral therapies combined with weight-loss medications or weight-loss surgery. In this article, we summarize the evidence of obesity management in treating T2DM and prediabetes.

Effect of valsartan on left ventricular anatomy and systolic function and aortic elasticity.

The objective of the study was to examine the effect of a 6-month daily treatment with 160 mg valsartan, an angiotensin II receptor blocker, on the left ventricular systolic function and aortic elasticity of patients with type 2 diabetes mellitus (T2DM) and healthy subjects. This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen healthy control subjects and 11 patients with T2DM were enrolled in the study. Eight control subjects and 4 T2DM patients completed the study. Cardiovascular magnetic resonance was used to evaluate the effect of valsartan on the left ventricular function and aortic elasticity. At baseline, T2DM patients had increased left ventricular mass (P = .006) when compared with the healthy controls. In the T2DM patients, treatment with valsartan, in comparison with receiving placebo, resulted in a reduction of aortic radius (P = .026) and wall thickness (P = .032) of the ascending aorta. In the abdominal aorta, valsartan treatment, when compared with placebo treatment, reduced the arterial compliance (P = .014) in the T2DM patients. Valsartan treatment for 6 months decreased the diameter and wall thickness of the ascending aorta in patients with T2DM, but may decrease AC of the abdominal aorta.

The endocrinopathies of anorexia nervosa.

OBJECTIVE: To describe the hormonal adaptations and alterations in anorexia nervosa. METHODS: We performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings. RESULTS: Anorexia nervosa is a devastating disease with a variety of endocrine manifestations. The effects of starvation are extensive and negatively affect the pituitary gland, thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. A thorough understanding of refeeding syndrome is imperative to nutrition rehabilitation in these patients to avoid devastating consequences. Although most endocrinopathies associated with anorexia nervosa reverse with recovery, short stature, osteoporosis, and infertility may be long-lasting complications. We describe a 20-year-old woman who presented with end-stage anorexia nervosa whose clinical course reflects the numerous complications caused by this disease. CONCLUSIONS: The effects of severe malnutrition and subsequent refeeding are extensive in anorexia nervosa. Nutrition rehabilitation is the most appropriate treatment for these patients; however, it must be done cautiously.

Obesity surgery: evidence for diabetes prevention/management.

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. Development of type 2 diabetes can be delayed or sometimes prevented from manifestation in individuals with obesity that are able to lose weight. Weight loss can be achieved either medically with behavioral therapies that combine diet and exercise treatment or with behavioral therapies combined with weight-loss medications or weight-loss surgery. There is strong evidence of an amelioration or resolution of type 2 diabetes in patients undergoing gastric bypass surgery. A recently published retrospective cohort study indicated that long-term total mortality from diabetes, heart disease, and cancer after gastric bypass surgery was substantially reduced. In this review, we summarize the evidence of surgical interventions in the treatment of type 2 diabetes.

Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women.

OBJECTIVE: The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women. DESIGN: This was a randomized, double-blind, placebo-controlled trial of menopausal women, aged 38 to 60 years, who experienced 4 to 14 hot flashes per day. After a 1-week run-in period, a total of 190 menopausal women were randomized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks. The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary. The secondary outcomes included changes in quality of life and hormonal profiles. RESULTS: A total of 147 women (77%) completed the study. It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally. At 8 weeks hot flash frequency was reduced by 43% in the 40-mg DRI group and by 41% in the 60-mg DRI group, compared with 32% in the placebo group (P = not significant vs placebo). The corresponding numbers for 12 weeks were 52%, 51%, and 39%, respectively (P = 0.07 and 0.09 vs placebo). When comparing the two treatment groups with the placebo group, there were significant reductions in mean daily hot flash frequency. The supplement (either 40 or 60 mg) reduced hot flash frequency by 43% at 8 weeks (P = 0.1) and 52% at 12 weeks (P = 0.048) but did not cause any significant changes in endogenous sex hormones or thyroid hormones. Menopausal quality of life improved in all three groups, although there were no statistically significant differences between groups. CONCLUSIONS: DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes.

Current perspectives of obesity and its treatment.

The prevalence of obesity and overweight is rising among adults and children. Ample evidence indicates that weight loss, even if moderate, can improve health status and lessen the incidence of obesity-related disease. A variety of treatments are available to deal with the condition. However, no matter what therapy is chosen, the patient must be aware that success may depend on adherence and follow-up with a health care practitioner.

The use of medical hyperspectral technology to evaluate microcirculatory changes in diabetic foot ulcers and to predict clinical outcomes.

OBJECTIVE: Foot ulceration is a serious complication of diabetes, and new techniques that can predict wound healing may prove very helpful. We tested the ability of medical hyperspectral technology (HT), a novel diagnostic scanning technique that can quantify tissue oxy- and deoxyhemoglobin to predict diabetic foot ulcer healing. RESEARCH DESIGN AND METHODS: Ten type 1 diabetic patients with 21 foot ulcer sites, 13 type 1 diabetic patients without ulcers, and 14 nondiabetic control subjects were seen up to 4 times over a 6-month period. HT measurements of oxyhemoglobin (HT-oxy) and deoxyhemoglobin (HT-deoxy) were performed at or near the ulcer area and on the upper and lower extremity distant from the ulcer. An HT healing index for each site was calculated from the HT-oxy and -deoxy values. RESULTS: Hyperspectral tissue oxygenation measurements observed changes in tissue immediately surrounding the ulcer when comparing ulcers that heal and ulcers that do not heal (P < 0.001). The sensitivity, specificity, and positive and negative predictive values of the HT index for predicting healing were 93, 86, 93, and 86%, respectively, when evaluated on images taken at the first visit. Changes in HT-oxy among the three risk groups were noted for the metatarsal area of the foot (P < 0.05) and the palm (P < 0.01). Changes in HT-deoxy and the HT healing index were noted for the palm only (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: HT has the capability to identify microvascular abnormalities and tissue oxygenation in the diabetic foot and predict ulcer healing. HT can assist in the management of foot ulceration.

Valsartan improves resting skin blood flow in type 2 diabetic patients and reduces poly(adenosine diphosphate-ribose) polymerase activation.

OBJECTIVE: To examine the effect of a 12-week daily treatment with 160 mg of valsartan, an angiotensin II receptor blocker, on the microcirculation and macrocirculation of type 2 diabetic patients (T2DM) and healthy subjects. METHODS: This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial. RESULTS: Treatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure, large vessel vascular reactivity, or carotid intima-media thickness. Resting skin blood flow increased by 60% (2%-90%; median and 25th-75th percentiles) during valsartan treatment and by only 2% (-22% to 27%) during placebo treatment (P < .05). No changes were observed in the nondiabetic subjects. Immunostaining studies of forearm skin biopsy samples from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose) polymerase (PARP) activity in 50% (6/12) of the subjects. PARP activity remained unchanged in placebo-treated subjects (P < .02). In addition, valsartan treatment increased CD31 staining in 33% (4/12) of the subjects, whereas no change was noted in sequential skin biopsy samples of placebo-treated subjects (P = .057). Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines, including CAMs, interleukin 6, tumor necrosis factor alpha, C-reactive protein, adiponectin, and plasma activator inhibitor 1. CONCLUSIONS: Valsartan increases the resting skin blood flow in T2DM, likely through reduction of PARP activity.

Early changes in the skin microcirculation and muscle metabolism of the diabetic foot.

BACKGROUND: Changes in the large vessels and microcirculation of the diabetic foot are important in the development of foot ulceration and subsequent failure to heal existing ulcers. We investigated whether oxygen delivery and muscle metabolism of the lower extremity were factors in diabetic foot disease. METHODS: We studied 108 patients (21 control individuals who did not have diabetes, 36 patients with diabetes who did not have neuropathy, and 51 patients with both diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to investigate the haemoglobin saturation (S(HSI)O2; % of oxyhaemoglobin in total haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and foot; we also used 31P-MRI scans to study the cellular metabolism of the foot muscles by measuring the concentrations of inorganic phosphate and phosphocreatine and calculating the ratio of inorganic phosphate to phosphocreatine (Pi/PCr). FINDINGS: The forearm S(HSI)O2 during resting was different in all three groups, with the highest value in controls (mean 42 [SD 17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups (p<0.0001). In the foot at resting, S(HSI)O2 was higher in the control (38 [22]) and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12]; p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p<0.0001). INTERPRETATION: Our results indicate that tissue S(HSI)O2 is reduced in the skin of patients with diabetes, and that this impairment is accentuated in the presence of neuropathy in the diabetic foot. Additionally, energy reserves of the foot muscles are reduced in the presence of diabetes, suggesting that microcirculation could be a major reason for this difference.

Foot small muscle atrophy is present before the detection of clinical neuropathy.

OBJECTIVE: To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 ((31)P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS: We studied 12 control subjects, 9 non-neuropathic diabetic patients, and 12 neuropathic diabetic patients using (31)P RARE and proton ((1)H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial (1)H and (31)P images. The average (31)P concentration across the metatarsal head region was measured from the (31)P images. RESULTS: The muscle area-to-total area ratio differed among all three groups (means +/- SD): 0.55 +/- 0.04 vs. 0.44 +/- 0.05 vs. 0.06 +/- 0.06 for control, non-neuropathic, and neuropathic subjects, respectively (P < 0.0001). The average (31)P concentration also differed among all groups: 27.7 +/- 3.8 vs. 21.7 +/- 4.8 vs. 7.9 +/- 8.8 mmol/l for control, non-neuropathic, and neuropathic subjects (P < 0.0001). The muscle area-to-total area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r = -0.83, P < 0.0001; vibration perception threshold, r = -0.79, P < 0.0001; and Semmes-Weinstein monofilaments, r = -0.87, P < 0.0001. CONCLUSIONS: Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The (31)P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems.

The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients.

We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (NID; endothelium independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin. Left ventricular function was evaluated using transthoracic echocardiogram. At the end of the 6-month period, a worsening in endothelium-dependent skin vasodilation (P = 0.02) and rise in endothelin levels (P = 0.01) were found in the vitamin E compared with the placebo group. At the end of the 12-month period, a worsening was observed in NID (P = 0.02) and a marginal worsening was seen in systolic blood pressure (P = 0.04) and FMD (P = 0.04) in the vitamin E compared with the placebo group. In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group (P = 0.05). No changes were observed in left ventricular function. We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients. Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects, the use of high dosages of vitamin E cannot be recommended.

Serum levels of interleukin-6 and C-reactive protein correlate with body mass index across the broad range of obesity.

BACKGROUND: It has been noted that elevated inflammatory markers, such as tumor necrosis factor-alpha (TNF), soluble TNF receptor II (sTNF-RII), interleukin 6 (IL-6) and C-reactive protein (CRP), are characteristically found in the serum in obese patients. In this study, we examined the correlation of these markers with BMI in nonobese, obese, and morbidly obese individuals to explore this relationship across the broad range of obesity. METHODS: A total of 9 nonobese, including normal and overweight (body mass index [BMI] <30 kg/m2) and 41 obese (BMI > or =30 kg/m2) adults were included in this study. Among obese subjects, 11 subjects were grade I or II obese (BMI > or =30 and <40 kg/m2), and 30 subjects were morbidly obese (grade III obese, BMI > or =40 kg/m2). Serum levels of glucose, insulin, TNF, sTNF-RII, IL-6, and CRP were measured. RESULTS: Obese subjects (BMI > or =30 kg/m2) had significantly higher serum levels of TNF, sTNF-RII, IL-6, and CRP compared with nonobese subjects. Serum levels of sTNF-RII, IL-6, and CRP, but not TNF, were positively correlated with BMI in obese subjects. However, in morbidly obese subjects, only the serum concentrations of IL-6 and CRP remained correlated with BMI, primarily because of this relationship in men. CONCLUSIONS: The present results support evidence that obesity represents an inflammatory state. In morbid obesity, the correlation of only IL-6 and CRP with BMI, particularly in males, suggests that IL-6 may be secreted in an endocrine manner in proportion to the expansion of fat mass particularly in the abdominal region, with a corresponding increase in hepatic production of CRP.

The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes.

We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk, prospective, randomized, placebo-controlled, double-blind clinical trial. The flow- mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (endothelium independent) in the brachial artery and the vascular reactivity at the forearm skin were measured. FMD improved in the atorvastatin-treated, at-risk subjects [median (25-75 percentile), 7.2% (2.9-9.6%) at exit visit vs. 6.6% (2.9-9.5%) at baseline; P < 0.05]. A similar improvement of FMD was found in atorvastatin-treated diabetic patients [median (25-75 percentile), 5.6 (3.9-7.9) at exit visit vs. 4.2 (3.2-7.2) at baseline; P = 0.07]. No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group. In the at-risk group, there was a decrease in the C-reactive protein [median (25-75 percentile), 0.12 mg/dl (0.07-0.27 mg/dl) at exit visit vs. 0.24 mg/dl (0.07-0.35 mg/dl) at baseline; P < 0.05] and TNF alpha [median (25-75 percentile), 2.6 pg/ml (1.8-4.1 pg/ml) at exit visit vs. 4.4 pg/ml (3.6-6.0 pg/ml) at baseline; P < 0.05] in the atorvastatin-treated patients, whereas in the diabetes group, a decrease in endothelin-1 (mean +/- SD, 0.97 +/- 0.29 pg/ml at exit visit vs. 1.19 +/- 0.42 pg/ml at baseline; P < 0.05) and plasminogen activator inhibitor-1 [median (25-75 percentile), 18 ng/ml (9-24 ng/ml) at exit visit vs. 27 ng/ml (7-41 ng/ml) at baseline; P < 0.05] were observed. We conclude that atorvastatin improves endothelial function and decreases levels of markers of endothelial activation and inflammation.

Kidney oxygenation during water diuresis and endothelial function in patients with type 2 diabetes and subjects at risk to develop diabetes.

The aim of the present study was to examine the relationship among water diuresis-induced changes in renal oxygenation, endothelial function, and various metabolic parameters in type 2 diabetic patients and healthy subjects at risk of type 2 diabetes. Thirty-eight subjects with type 2 diabetes (D: age, 54 +/- 10 years, mean +/- SD, 24 men) and 7 healthy subjects with parental history of type 2 diabetes or with impaired glucose tolerance (IGT) (relatives [R]: age 46 +/- 11 years, 4 men) were included. Laser Doppler imaging scanning was used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (Ach) and 1% sodium nitroprusside (SNP), and ultrasound was used to measure the flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) in the brachial artery. Renal oxygenation was assessed by magnetic resonance imaging (MRI) before and during water diuresis. A decrease in the magnetic parameter R2* implies an increase in oxygenation. Renal medullary oxygenation did not improve with diuresis in either group (D: -0.5 +/- 1.9, R: -0.4 +/- 2.1, P = not significant [NS]). The renal cortical oxygenation showed a small, but statistically significant, improvement after diuresis in the 2 groups (D: -0.6 +/- 1.1, R: -0.5 +/- 0.5, P <.05). There were no correlations between the change in cortical R2* (R2* post-minus R2* prewater diuresis) and the micro- and macrovascular reactivity. The postdiuresis renal cortical R2* was negatively correlated with both the Ach- and SNP-induced skin vasodilation (% change over baseline)(r = -.40, P <.01 and r = -.39, P <.05, respectively), while no correlation existed with the FMD and NID. The baseline renal cortical oxygenation was also negatively correlated with the SNP-induced skin vasodilation (r = -.36, P <.05) and positively correlated with the fasting plasma glucose, total cholesterol, and vascular cell adhesion molecule (VCAM) concentrations (r =.34, P <.05, r =.31, P <.05 and r =.37, P <.05, respectively). These preliminary findings suggest an association between the kidney cortical oxygenation and the skin microvascular reactivity, glycemia, and lipidemia. Water diuresis failed to produce an improvement in renal medullary oxygenation in both patients with diabetes and subjects at risk for diabetes.

Enhancing sensation in diabetic neuropathic foot with mechanical noise.

OBJECTIVE: Localized low-level mechanical or electrical noise can significantly enhance tactile sensitivity in healthy young subjects and older adults. This phenomenon is termed stochastic resonance (SR). In this study, we examined the effect of SR on vibratory and tactile sensation in patients with moderate to severe diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 20 subjects were included in the study. The vibration perception threshold (VPT) test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of the left foot and the big toe were determined under two mechanical noise stimulus conditions: null (no noise) condition and at 10% lower than each subject's mechanical noise threshold of perception. RESULTS: The baseline values (mean +/- SD) were as follows: Neuropathy Symptom Score (NSS) 5.2 +/- 2.5, Neuropathy Disability Score (NDS) 5.0 +/- 2.1, VPT 24 +/- 11 V, and SWF threshold 5.6 +/- 0.8 at the plantar surface of the foot and 5.3 +/- 0.9 at the big toe. The VPT improved significantly from 24 +/- 11 under null condition to 19 +/- 10 V with mechanical noise (P < 0.0001). Mechanical noise also significantly increased the number of detections of the SWF at the plantar surface of the foot (detection rate 66 +/- 11 vs. 59 +/- 15%, P < 0.02) but not at the big toe (63 +/- 10 vs. 61 +/- 16%, P = NS). CONCLUSIONS: Mechanical noise stimulation improves vibration and tactile perception in diabetic patients with moderate to severe neuropathy. Additional studies are required to examine the effect of long-term noise stimulation on parameters of nerve function.