Evolving concepts on the role of dyslipidemia,bioenergetics, and inflammation in the pathogenesis and treatment of diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most widespread and disabling neurological conditions, accounting for half of all neuropathy cases worldwide. Despite its high prevalence, no approved disease modifying therapies exist. There is now a growing body of evidence that DPN secondary to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) represents different disease processes, with T2DM DPN best understood within the context of metabolic syndrome rather than hyperglycemia. In this review, we highlight currently understood mechanisms of DPN, along with their corresponding potential therapeutic targets. We frame this discussion within a practical overview of how the field evolved from initial human observations to murine pathomechanistic and therapeutic models into ongoing and human clinical trials, with particular emphasis on T2DM DPN and metabolic syndrome.     

Sensory and motor axonal excitability testing in early diabetic neuropathy

ObjectiveThe aim of the present study was to gain insight into the pathophysiology of diabetic polyneuropathy (DPN) and examine the diagnostic value of sensory and motor axonal excitability testing.MethodsOne hundred and eleven type 2 diabetics with and without DPN (disease duration: 6.36 ± 0.25 years) and 60 controls were included. All participants received a thorough clinical examination including Michigan Neuropathy Screening Instrument (MNSI) score, nerve conduction studies (NCS), and sensory and motor excitability tests. Patients were compared by the likelihood of neuropathy presence, ranging from no DPN (17), possible/probable DPN (46) to NCS-confirmed DPN (48).ResultsMotor excitability tests showed differences in rheobase and depolarizing threshold electrotonus measures between NCS-confirmed DPN group and controls but no changes in hyperpolarising threshold electrotonus or recovery cycle parameters. Sensory excitability showed even less changes despite pronounced sensory NCS abnormalities. There were only weak correlations between the above motor excitability parameters and clinical scores.ConclusionsChanges in excitability in the examined patient group were subtle, perhaps because of the relatively short disease duration.SignificanceLess pronounced excitability changes than NCS suggest that axonal excitability testing is not of diagnostic value for early DPN and does not provide information on the mechanisms.     

Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Zenarestat Study Group.

OBJECTIVE: To determine whether the aldose reductase inhibitor (ARI) zenarestat improves nerve conduction velocity (NCV) and nerve morphology in diabetic peripheral polyneuropathy (DPN). METHODS: A 52-week, randomized, placebo-controlled, double-blinded, multiple-dose, clinical trial with the ARI zenarestat was conducted in patients with mild to moderate DPN. NCV was measured at baseline and study end. Contralateral sural nerve biopsies were obtained at 6 weeks and at the study's end for nerve sorbitol measurement and computer-assisted light morphometry to determine myelinated nerve fiber density (number of fibers/mm2 cross-sectional area) in serial bilateral sural nerve biopsies. RESULTS: Dose-dependent increments in sural nerve zenarestat level and sorbitol suppression were accompanied by significant improvement in NCV. In a secondary analysis, zenarestat doses producing >80% sorbitol suppression were associated with a significant increase in the density of small-diameter (<5 microm) sural nerve myelinated fibers. CONCLUSIONS: Aldose reductase pathway inhibition improves NCV slowing and small myelinated nerve fiber loss in DPN in humans, but >80% suppression of nerve sorbitol content is required. Thus, even low residual levels of aldose reductase activity may be neurotoxic in diabetes, and potent ARIs such as zenarestat may be required to stop or reverse progression of DPN.     

Motor end plate innervation loss in diabetes and the role of insulin

Retraction of distal sensory axons is a prominent feature in diabetic peripheral neuropathy (DPN), a process amenable to insulin therapy. Nevertheless, diabetic patients and long-term diabetic mice develop motor deficits after longer durations of DPN, a process that may be related to insulin deficiency. To compare the efficacy of intranasal delivery of insulin (IN-I) and subcutaneous insulin (Subc-I) in preventing motor deficits in a long-term mouse model of DPN, IN-I or Subc-I, 0.87 IU daily or placebo was delivered in separate cohorts of diabetic and nondiabetic CD1 mice for 8 months. Radiolabeled detection was used to assess insulin delivery and biodistribution. Biweekly behavioral tests and monthly electrophysiological and multipoint quantitative studies assessed motor function deficits. Morphometric analysis of spinal cord, peripheral nerve, muscle innervation, and specific molecular markers were evaluated at and before the end point. Despite progressive distal axonal terminal loss, numbers and caliber of motor neurons were preserved. There were no differences in glycemia between IN-I and Subc-I-treated mice. Intranasal delivery of insulin and, to a lesser extent, Subc-I, protected against electrophysiological decline, loss of neuromuscular junctions, and loss of motor behavioral skills. Intranasal delivery of insulin was associated with greater preservation of the phosphatidylinositol 3-kinase signaling pathway involving Akt, cyclic AMP response element binding protein,and glycogen synthase kinase 3β but did not alter extracellular signal-regulated kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase, or c-Jun amino-terminal kinase. Thus, direct delivery of insulin to the nervous system might prevent motor deficit in human type 1 diabetes by preservation of the phosphatidylinositol 3-kinase-Akt pathway rather than only affecting glycemic levels; the effects of insulin on other signaling pathways may, however, play additional roles.     

Improvement of cutaneous sensitivity in diabetic peripheral neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate

Studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that these B vitamins may reverse both the symptoms and the pathophysiology of diabetic peripheral neuropathy (DPN). The efficacy of oral-combination L-methylfolate, 3 mg; methylcobalamin, 2 mg; and pyridoxal 5'-phosphate, 35 mg (LMF-MC-PP) in restoring cutaneous sensitivity in patients with type 2 diabetes with DPN was evaluated in 20 type 2 diabetic patients who were given LMF-MC-PP twice daily for 4 weeks and then once daily for an additional 48 weeks. Statistically significant improvement in 1-point (tactile) and 2-point (discriminatory) static testing at the right and left great toe and heel in the patients was observed in all 3 follow-up periods: 1) baseline to 6 months, 2) baseline to 1 year, and 3) 6 months to 1 year. The greatest improvement occurred between baseline and 1 year of treatment. Treatment with oral LMF-MC-PP appears to promote restoration of lost cutaneous sensation in DPN.     

Aerobic exercise improves measures of vascular health in diabetic peripheral neuropathy

Aims: Aerobic exercise improves vascular endothelial function in people with Type 2 diabetes mellitus (T2DM). There is minimal information available regarding vascular health in people with T2DM and diabetic peripheral neuropathy (DPN). Thus, the primary aim of this secondary analysis was to determine whether a 16-week aerobic exercise intervention could improve vascular health in people with T2DM and DPN. A secondary aim was to explore the relationship between changes in flow-mediated dilation (FMD) and the number of years since diagnosis of DPN. Methods: We examined whether a 16-week aerobic exercise intervention would improve vascular health in people with T2DM and DPN. We used Doppler ultrasound to assess brachial artery diameter and peak shear at baseline and post-exercise. Paired t-tests were used to determine whether the outcome measures improved from baseline to post-intervention. Pearson correlation assessed the relationship between DPN (years) and the percent change score (pre- to post-intervention) for FMD. Results: Seventeen individuals were included in the data analysis. After the intervention, peak diameter increased (3.9 (0.5) to 4.0 (0.5) mm; p = 0.07). Time to peak shear occurred at 60.5 (24.6) seconds when compared to baseline at 68.2 (22.7) seconds; p = 0.17. We found that a longer duration (in years) of DPN demonstrated a fair, negative relationship (r = ?0.41, p = 0.19) with the percent change in FMD. Conclusion: Aerobic exercise was beneficial for improving measures of vascular health but these were not statistically significant. The magnitude of change may be affected by the duration of DPN.     

Sural sensory action potential identifies diabetic peripheral neuropathy responders to therapy

Identifying patients with diabetic peripheral neuropathy (DPN) amenable to therapy is a challenge. To determine whether the amplitude of the sural sensory nerve action potential (sural SNAP) reflects the severity of DPN, an analysis was performed on 205 patients with DPN, identified by an abnormal vibration detection threshold (VDT), who were enrolled in a multinational clinical trial investigating ruboxistaurin (RBX) mesylate. Nerve conduction velocity and response amplitude and latency were measured and compared. VDT was significantly lower in those with preserved sural SNAPs (n = 128) than in those in whom they were absent (n = 77; 21.5 vs. 22.7 JND units, P = 0.002). Thus, preserved sural SNAP denoted less severe DPN. Logistic regression analyses evaluating baseline characteristics, HbA(1c), and baseline symptom scores identified only DPN duration as a factor that might contribute to the presence of sural SNAP (P = 0.004; OR = 0.896). For patients with abnormal VDT, preserved sural SNAP identifies a patient population with less severe DPN who may respond to therapeutic intervention in clinical trials.     

糖尿病病程对糖尿病下肢周围神经病变的影响

目的探讨糖尿病（DM）病程对糖尿病周围神经病变（DPN）严重程度及下肢周围神经显微减压术疗效的影响,以及糖尿病周围神经病变早期诊断、早期手术的意义。方法以5年糖尿病痛程作为标准,将我科近年收治的1526例糖尿痛周围神经病患者分为短DM病程组和长DM病程组,按Dellon术式对卡压的神经进行下肢周围神经显微减压术。所有患者术前、术后1.5年进行神经高频超声、定量感觉检查（QST）、神经感觉传导速度（NCV）检测,并选取50例正常人群作为对照组检测相同指标。结果与对照组相比,DPN患者的NCV、冷感觉阈值较低,热感觉阈值、振动觉阈值及神经横断面积（CSA）较高,差异有统计学意义（P〈0．05）。患者术后各项指标明显改善,与术前相比,差异有统计学意义（P〈0．05）。短DM病程DPN患者术前和术后各指标均优于长DM病程DPN患者,两组比较差异有统计学意义（P〈0．05）。短DM病程DPN患者NCV阳性检测率为71．5％,QST阳性检测率为93．7％;长DM病程DPN患者NCV阳性检测率为90．3％,QST阳性检测率为95．3％。结论糖尿病痛程对DPN患者发病时的严重程度至关重要,同时也对DPN患者的手术疗效和预后产生影响。DPN的早期诊断、早期手术具有重要临床价值。     

Local insulin and the rapid regrowth of diabetic epidermal axons

Insulin deficiency may contribute toward the neurological deficits of diabetic polyneuropathy (DPN). In particular, the unique trophic properties of insulin, acting on sensory neuron and axon receptors offer an approach toward reversing loss of skin axons that develops during diabetes. Here we examined how local cutaneous insulin, acting on axon receptors, influences innervation of the epidermis. That cutaneous axons might be amenable to regrowth was suggested by confirming that a high proportion of epidermal axons expressed GAP43/B50, a growth associated protein. Also, IRβ (insulin receptor subunit β) mRNA was expressed and upregulated in the footpads of diabetic mice and protein expression was upregulated in their sensory dorsal root ganglia. Moreover, footpads expressed mRNAs of the downstream insulin transduction molecules, IRS-1 and IRS-2. IRβ protein was identified in dermal axons, some epidermal sensory axons, and in keratinocytes. In separate models of experimental diabetes, we identified a surprising and rapid local response of this axon population to insulin. C57BL/6J streptozotocin (STZ) injected mice, as a model of type 1 diabetes and dbdb mice, as a model of type 2 diabetes were both evaluated after 3 months of diabetes duration. Local hindpaw plantar injections of low dose subhypoglycemic insulin (that did not alter diabetic hyperglycemia) and carrier (into the opposite paw) were given over two days and innervation studied at 5 days. Insulin injections in both models were associated with an ipsilateral rise in the density of PGP 9.5 labeled diabetic epidermal axons at 5 days, compared to that of their contralateral carrier injected hindpaw. Nondiabetic controls did not have changes in innervation following insulin. In a separate cohort of STZ diabetic mice and controls evaluated for paw sensation, there was mild improvement in mechanical, but not thermal sensation at 2 weeks after insulin injection in diabetics but not controls. Fine unmyelinated epidermal axons have considerable plasticity. Here we identify a rapid improvement of skin innervation by doses of insulin insufficient to alter glycemia or innervation of the opposite paw. Local direct insulin signaling of receptors expressed on diabetic cutaneous axons may reverse retraction of their branches during experimental DPN.     

HLA class Ⅱ alleles and risk for peripheral neuropathy in type 2 diabetes patients

The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. hTis study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 andP = 0.05 respectively). Also, patients with severe neurop-athy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our ifndings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.     

Risk of suicidal ideation in diabetes varies by diabetes regimen,diabetes duration,and HbA1c level

Objective

To investigate patient subgroups based on the clinical characteristics of diabetes to evaluate risk factors for suicidal ideation using a large population-based sample in South Korea.

Methods

Data from the Fifth Korea National Health and Nutrition Examination Survey, a cross-sectional, nationally representative survey, were analyzed. The participants were 9159 subjects aged ≥ 40 years. We defined patients with diabetes based on self-reported physician-diagnosed diabetes. We evaluated clinical risk factors for suicidal ideation according to diabetes regimen, diabetes duration, and glycated hemoglobin (HbA1c) level compared with no diabetes. Given the complex sample design and unequal weights, we analyzed weighted percentages and used survey logistic regression.

Results

Diabetes per se was not associated with suicidal ideation. However, suicidal ideation was significantly more prevalent among patients who had injected insulin, had a duration of diabetes ≥ 5 years and had HbA1c levels ≥ 6.5 compared with those without diabetes. Depressive symptoms were the most prominent predictor of suicidal ideation.

Conclusions

Insulin therapy, diabetes of long duration, and unsatisfactory glycemic control were identified as risk factors for suicidal ideation; thus, patients with these characteristics warrant special attention. Our findings suggest the need to integrate efforts to manage emotional distress into diabetes care.     

F波在糖尿病性周围神经病中的诊断价值

目的 探讨F波在糖尿病性周围神经病（DPN）中的诊断价值。方法 测定106例糖尿病患者和75名正常人的下肢F波最短潜伏期、时限、波幅和面积，以及M波波幅和面积。结果 （1）无周围神经病变的糖尿病患者30例，F波时限增宽8例，F波最短潜伏期延长4例，F/M波面积增大2例。（2）有周围神经病变的糖尿病患者76例，F波最短潜伏期均延长；F/M波波幅和F/M波面积均增大；F波时限在轻型DPN患者中增宽，在重型DPN患者中未见明显异常。（3）正常人F波最短潜伏期上限（Y）与腿长（X）的函数关系为Y=12.3 48.8X^2。结论 （1）F波作为早期诊断DPN的敏感指标，并可发现亚临床DPN。（2）在DPN患者中，远端神经节段尚未发生病变时，即可出现近端神经节段病变，提示血管因素在DPN发病机制中的作用。     

2型糖尿病患者合并周围神经病变相关危险因素分析

目的 探讨2型糖尿病周围神经病变的相关危险因素.方法 选取2型糖尿病（DM）患者114例为研究对象,根据有无合并周围神经病变将其分为糖尿病周围神经病变组（DPN组）和非糖尿病周围神经病变组（NDPN组）.分析患者临床资料,探讨2型糖尿病周围神经病变相关因素.结果 （1） DPN组与NDPN组病患年龄、病程、FPG、2hPG、HbA1C、尿 A/C 差异均有统计学意义（P〈0.05）.（2）Logistic分析显示糖尿病病程、年龄、糖化血红蛋白（HbA1C）是糖尿病周围神经病变的独立危险因素.结论 糖尿病病程、年龄、空腹血糖、餐后 2 h血糖、糖化血红蛋白等是 2 型糖尿病并周围神经病变的相关危险因素.其中年龄大、病程长、高HbA1C的糖尿病患者发生 DPN 的风险增加.提示临床医生应在糖尿病早期对DPN和相关危险因素进行预防和干预.     

Sleep duration is associated with an increased risk for the prevalence of type 2 diabetes in middle-aged women - The FIN-D2D survey

OBJECTIVE: To examine the association between sleep duration with type 2 diabetes and abnormal glucose tolerance among middle-aged men and women in Finland. METHODS: The FIN-D2D survey is a population-based cross-sectional multicentre study in Finland, with 1336 men and 1434 women aged 45-74 participating in the survey during 2004 and 2005. A health examination including an oral glucose tolerance test and sleep questionnaire was performed for all participants. RESULTS: There was an independent association between abnormal sleeping times and type 2 diabetes in middle-aged women. Even after adjustments for age, body mass index, sleep apnea probability, smoking, physical activity, and central nervous system-affecting medication, sleep duration of 6h or less or 8h or longer was independently associated with type 2 diabetes. There was no increase in the prevalence of diabetes in middle-aged men with abnormal sleeping times. CONCLUSION: Short (< or = 6h) or long (> or = 8h) sleep duration is related to an increased risk of type 2 diabetes in middle-aged women but not in men.     

Altered expression of IRS2 and GRB2 in demyelination of peripheral neurons: Implications in diabetic neuropathy

Demyelination of the peripheral nerves and dysfunction of Schwann cells (SCs) are the chronic complications involved in the development of peripheral neuropathy among diabetic patients. Insulin signaling plays an important role in restoring the myelin proteins in diabetic peripheral neuropathy (DPN). Since insulin levels are altered in diabetes, it becomes of great interest to appreciate the role and regulation of docking and adaptor protein, how these proteins respond to variations in the levels of insulin as experienced in juvenile diabetes. Tyrosine phosphorylation of receptor protein kinases provides a docking site for the activation of adaptor proteins which are the key regulators of insulin signaling pathway. In this report, we studied the long term effect of insulin as a neurotrophic factor and identified the isoform of receptor substrate involved in the propagation of insulin signal in SCs. We also studied the ability of insulin to regulate the expression of different receptor substrates like insulin receptor substrate-1 (IRS1), insulin receptor substrate-2 (IRS2) and growth factor receptor-bound protein-2 (GRB2) that propagate the insulin signaling and also their variation in hyperglycemic SCs and sciatic nerve of the diabetic rats. Results confirmed that IRS2 is the key receptor substrate involved in insulin signal transduction. But, a radical increase in the phosphorylation of IRS2 at serine 731 prevents the recruitment of GRB2 adaptor protein which may fail further to connect the Ras and other pathways required to the cell for its survival and to maintain integrity. These findings prove that SCs and sciatic nerve express IRS proteins that are altered by diabetes and thereby insulin signaling downstream is impaired and that contribute to the pathogenesis of DPN.     

依达拉奉与甲钴胺联合治疗糖尿病周围神经病变

目的观察依达拉奉(必存)与甲钴胺(弥可保)联合治疗糖尿病周同神经病变(DPN)的疗效。方法将128例患者随机分为治疗组(66例)和对照组(62例),均以糖尿病教育,控制饮食,胰岛素严格控制血糖稳定基础上,治疗组给予依达拉奉与甲钴胺,对照组给予丹参与甲钴胺治疗,连用2周。结果治疗组DPN症状体征,神经传导速度改善明显高于对照组。结论依达拉奉与甲钴胺联用可明显改善DPN的治疗效果。     

Insulin deficiency rather than hyperglycemia accounts for impaired neurotrophic responses and nerve fiber regeneration in type 1 diabetic neuropathy

Diabetic polyneuropathy (DPN) shows more severe functional and structural changes in type 1 than in type 2 human and experimental diabetes. We have previously suggested that these differences may be due to insulin and/or C-peptide deficiencies in type 1 diabetes. To further explore these differences between type I and type 2 DPN, we examined factors underlying nerve fiber regeneration in the hyperinsulinemic type 2 BB/Z-rat and compared these with previous data obtained from the iso-hyperglycemic, insulin and C-peptide-deficient type 1 diabetic BB/Wor-rat. The expression of neurotrophic factors and cytoskeletal proteins were studied in L4 and L5 dorsal root ganglia (DRG) at various time points after sciatic nerve crush. The data were compared to those of nondiabetes-prone BB-rats. Insulin-like growth factor 1 (IGF-1) and TrkA levels were lower in DRG from type 1 than from those of type 2 and control BB-rats. On the other hand, IGF-1 receptor expression was increased at baseline in type 1 BB/Wor-rats and decreased after crush injury, whereas its expression increased after crush injury in both control and type 2 BB/Z-rats. Following crush injury, betaII- and betaIII-tubulins were upregulated in type 2 BB/Z and control rats, which did not occur in type 1 BB/Wor-rats. Furthermore, type 2 BB/Z-rats showed the normal downregulation of low and medium molecular neurofilament (NF-L and NF-M, respectively), which did not occur in type 1 BB/Wor-rats. These findings were associated with significantly milder abnormalities in axonal elongation and caliber growth of regenerating fibers in type 2 compared to type 1 diabetic rats. These data suggest that impaired insulin signaling in type 1 diabetic nerve may be of greater significance in the regulation of neurotrophic and neurocytoskeletal protein synthesis than hyperglycemia in explaining the differences in nerve fiber regeneration between type 2 and type 1 diabetes.     

Validation of Michigan neuropathy screening instrument for diabetic peripheral neuropathy

OBJECTIVE: The reliability and accuracy of the Michigan neuropathy screening instrument (MNSI) have been discussed recently. As a result of the difficulties of performing and analyzing nerve biopsy as a standard diagnostic test, electromyography and neuronography is used as the best alternative diagnostic procedure. The objective of this study was to determine the diagnostic performance of the test characteristics and cut-off point of MNSI scoring for the diagnosis of diabetic peripheral neuropathy. METHOD: Over a 2-year period, a cross-sectional study was conducted on 176 type 2 diabetic patients. An internist carried out the MNSI and the sum of scores varying from 0 to 1 for each abnormality as revealed in foot appearance, ulceration, ankle reflexes and vibratory perception has been recorded. A neurologist, who was blind to the MNSI scores, performed all neurophysiological studies. The test performance characteristics of the MNSI procedure were measured for different cut-off values. RESULTS: MNSI scores of 1.5, 2.0, 2.5 and 3.0 were assessed as cut-off values. Sensitivities were 79%, 65%, 50% and 35% and specificities were 65%, 83%, 91% and 94%, respectively. Positive predictive values increased and negative predictive values decreased for each score. Accuracies, likelihood ratios and post-test probabilities were measured. CONCLUSION: The accuracy of MNSI scoring makes it a useful screening test for diabetic neuropathy in taking a decision regarding which patients should be referred to a neurologist for electrophysiological studies. High specificity, likelihood ratios over 5 and a moderate to good post-test probability give a high diagnostic impact for MNSI scoring. We suggest a cut-off point of 2 for the MNSI procedure. However, electrophysiological studies should be considered when the patient has signs and symptoms other than those rated by the MNSI, suggesting peripheral nerve involvement, and also because the MNSI is still just a screening test.     

Ethnic-specific associations of sleep duration and daytime napping with prevalent type 2 diabetes in postmenopausal women

ObjectiveThe objective of this study was to evaluate ethnic differences in the associations of nighttime sleep and daytime napping durations with prevalent type 2 diabetes.MethodsSamples of White (n = 908), Filipina (n = 330), and Black (n = 371) community-dwelling, postmenopausal women aged 50–86 years were evaluated with cross-sectional data obtained during 1992–1999 including self-reported duration of nighttime sleep and daytime napping, behaviors, medical history, and medication use. The prevalence of type 2 diabetes was evaluated with a 2-h 75-g oral glucose tolerance test.ResultsOverall, 10.9% of White, 37.8% of Filipina, and 17.8% of Black women had type 2 diabetes. Average sleep durations were 7.3, 6.3, and 6.6 h and napping durations were 16.8, 31.7, and 25.9 min for White, Filipina, and Black women, respectively. Sleep duration showed a significant (p < 0.01) nonlinear association with type 2 diabetes in Filipina women, with increased odds of diabetes at both low and high sleep durations independent of age, body mass index (BMI), triglyceride to high-density lipoprotein (HDL) ratio, hypertension, and daytime napping duration. Daytime napping duration was associated with type 2 diabetes only among White women; those napping ≥ 30 min/day had 74% (95% confidence interval (CI) = 10%, 175%) higher odds of diabetes compared to non-nappers independent of covariates including nighttime sleep duration.ConclusionsResults suggest ethnic-specific associations of nighttime sleep and daytime napping durations with type 2 diabetes.     

Possible Role Of Uncoupling Proteins As Protectors From Hyperglycemia-Induced Neuropathy

Diagnosis of carpal tunnel syndrome (CTS) in patients with diabetic polyneuropathy (DPN) is important as therapeutic interventions directed towards relief of CTS may be effective irrespective of DPN. The frequency of clinical CTS and the best electrodiagnostic discriminator of CTS from diffuse neuropathy are uncertain. 478 subjects including reference, non-neuropathic subjects with diabetes mellitus (DM), and diabetic patients with mild, moderate and severe neuropathy were evaluated for clinical features of CTS. All subjects had routine determinations of median nerve distal motor and sensory latencies, sensory and motor potential amplitudes and sensory conduction velocities. Other parameters tested were: ratios of median to ulnar nerve distal motor and sensory latencies, distal motor and sensory amplitudes, and distal conduction velocities. Similar median to sural nerve ratios for sensory latencies, amplitudes and conduction velocities were determined as were ratios of median nerve motor amplitudes and latencies to sural nerve parameters. Segmental median sensory nerve conduction velocities were evaluated. The frequency of clinical CTS was 2% in the reference population, 14% in diabetic patients without DPN, and 30% in those with DPN. We did not find any reliable electrodiagnostic discriminator for CTS in patients with DM +/− DPN. Some of the parameters worsened with severity of neuropathy, but none reliably distinguished diabetic patients with and without CTS. Given that CTS is frequent in patients with DPN, but electrodiagnostic criteria cannot distinguish those with clinical CTS, a trial of therapy may be indicated in these patients regardless of the electrodiagnostic findings.