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Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04-7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN., (© 2024. The Author(s).)

Objectives: Cardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke)., Methods: In this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE., Results: The overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio., Conclusions: Besides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Diabetic sensory neuropathy has rarely been studied in the Asian populations. This study investigated the prevalence and risk factors of sensory symptoms (SS) in the Taiwanese diabetes patients., Methods: A total of 1,400 diabetes patients received a health examination together with a structured questionnaire interview for three categories of abnormal sensation of numbness or tingling pain, electric shock, and skin thickness sensation on seven anatomical sites on upper limbs and six sites on lower limbs. Prevalence of SS was defined using nine different criteria, with the least stringent criterion of "any positive symptom on at least 1 site" and the most stringent criterion of "any positive symptom on at least bilateral and symmetrical 2 sites involving the lower limb." Logistic regression was used to estimate the odds ratios and their 95% confidence interval for SS by the different definitions. Fasting plasma glucose and hemoglobin A 1c were entered in separate models to avoid hypercollinearity., Results: The prevalence of SS was 14.4 and 54.0% when using the most stringent and least stringent criterion, respectively. Women consistently had a significantly higher prevalence than men did. Among the three categories of symptoms, numbness or tingling pain was the most common, and fingers and toes were the most commonly involved anatomical sites. For any symptoms, 37.1% of the patients had any symptoms on the upper limbs and 41.7% had any symptoms on the lower limbs. Female sex, diabetes duration, hemoglobin A 1c , and hypertension were associated with SS in all models., Conclusions: Taiwanese diabetes patients may have a high prevalence of SS if a structured questionnaire is used for screening. Female sex, diabetes duration, hemoglobin A 1c , and hypertension are associated with SS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tseng, Chong and Sheu.)

Objective: To examine whether variations in fasting plasma glucose (FPG), as measured by the coefficient of variation (CV), is a predictor of diabetic polyneuropathy (DPN) risk, considering glycated hemoglobin (HbA1c) and other traditional risk factors., Methods: Type 2 diabetic patients enrolled in the National Diabetes Care Management Program were ≥30 years of age and free of DPN (n = 36,152). They were enrolled in 2002-2004 and were monitored until 2011. The related factors were analyzed using Cox proportional hazards regression models., Results: During an average 7.23 years of follow-up, a total of 7,219 incident cases of DPN were identified, with a crude incidence rate of 27.62/1,000 person-years (25.83 for men and 29.31 for women). After multivariate adjustment, both FPG-CV and HbA1c were significant predictors of DPN, with corresponding hazard ratios of 1.14 (95% confidence interval [CI] 1.05-1.23) and 1.15 (95% CI 1.06-1.24) for FPG-CV in the fourth to fifth quintiles and 1.13 (95% CI 1.07-1.20) for HbA1c ≥7%. This finding maintained consistency after excluding potential confounders in the sensitivity analysis, further validating the results., Conclusions: FPG-CV and HbA1c ≥7% were potent predictors of DPN in type 2 diabetic patients. The associations among HbA1c, glycemic variability, and DPN suggest a linked pathophysiologic mechanism, which may play a crucial role in clinical risk assessments., (© 2017 American Academy of Neurology.)

This study looked at spectral analysis of heart rate variability (HRV) between patients with type 2 diabetes mellitus (DM) and healthy controls. The association between diabetic autonomic neuropathy (DAN) with HRV parameter changes and DM risk factors (including nephropathy) was investigated. HRV parameters were compared between 271 patients with DM and 160 controls. A statistically significant difference was found between the two groups for each parameter. Patients with DM were then divided into three groups by the levels of individual risk factors: body mass index, total cholesterol, 2-h postprandial plasma glucose concentration, glycosylated haemoglobin, duration of DM and the albumin-creatinine ratio. HRV parameters decreased significantly in patients with DM as the risk factor level progressed. This study identified previously known and new potential risk factors for the development of DAN, which may be important for the development of risk reduction strategies.

This study examined healthcare costs for medication-using diabetic patients in Taiwan and predicted which factors were associated with costs. We analyzed claims data from the National Health Insurance (NHI) program in Taiwan from 1998 to 1999. The approach included estimates of costs attributable to diabetes, diabetes-related complications, comorbidity incurred by diabetic patients. A multiple regression model was used to assess the contribution of patients' characteristics in 1998 on outpatient, inpatient, and total costs in 1998 and 1999. The prevalence of medication-using patients with diabetes was 2.6% in 1998 and 2.8% in 1999. Costs of healthcare were 13.3% of total costs of NHI in 1998 versus 13.0% in 1999. Health services delivered near the end of life consumed large portions of medical dollars. The three most prevalent clinical associations of diabetes were congestive heart failure, neuropathy, and ischemic heart disease. Adjusted for demographic and clinical characteristics in 1998, this model could explain 8.0, 9.3, and 12.5%, respectively, of the cost variation in outpatient, inpatient, and total costs in 1999.

From July 1988 to June 1989, the etiology was registered of 520 patients with generalized neuropathy in 5 neurological centers in Taiwan. The neuropathy was diabetic in 256 cases (49.23%), alcoholic in 45 (8.65%), inflammatory in 34 (6.53%; including 21 with acute inflammatory demyelinating polyneuropathy, 12 with chronic inflammatory demyelinating polyneuropathy, and 1 with chronic relapsing polyneuropathy), 12 with associated malignancy (2.31%), 9 with dysproteinemia (1.73%), uremic in 22 (4.23%), hereditary motor and sensory in 22 (4.23%), toxic in 14 (2.69%), ischemic in 12 (2.31%), hypothyroidism in 10 (1.92%), nutritional deficiency and malabsorption in 6 (1.15%), chronic liver disease in 4 (0.77%), other diseases in 11 (2.12%) and unclassified in 63 (12.12%). This survey provided a crude etiological picture of generalized neuropathy on this island.