Spectrum of Diabetic Neuropathy: New Insights in Diagnosis and Treatment.

Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.

Cardiovascular Autonomic Neuropathy and Risk of Kidney Function Decline in Type 1 and Type 2 Diabetes: Findings From the PERL and ACCORD Cohorts.

Results of previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among people with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N = 469) and with type 2 diabetes (T2D) from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (N = 7,973). Baseline CAN was ascertained with electrocardiogram-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss of ≥5 mL/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed-effects, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 mL/min/1.73 m2/year (95% CI -1.93 to -0.37; P = 4.0 × 10-3) in PERL and 0.34 mL/min/1.73 m2/year (95% CI -0.49 to -0.19; P = 6.3 × 10-6) in ACCORD. This translated to 2.11 (95% CI 1.23-3.63; P = 6.9 × 10-3) and 1.39 (95% CI 1.20-1.61; P = 1.1 × 10-5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (hazard ratio 2.60 [95% CI 1.15-5.45], P = 0.02, in PERL and hazard ratio 1.54 [95% CI 1.28-1.84], P = 3.8 × 10-6, in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help with development of new therapies to prevent kidney function decline in patients with diabetes.

Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D).

AIMS: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D. METHODS: Pilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period. RESULTS: Forty-five T2D participants on metformin monotherapy (mean age 57 ±â€¯8 years, duration 7 ±â€¯6 years, HbA1c 7.8 ±â€¯1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride. CONCLUSIONS: Short term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN. CLINICAL TRIAL REGISTRATION: NCT02973477.

Cardiovascular autonomic neuropathy: A silent killer with long reach.

Cardiovascular autonomic neuropathy (CAN) is a common and deadly complication of diabetes mellitus, which is frequently overlooked in clinical practice due to its characteristic subtle presentation earlier in disease. Yet, timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including cardiovascular disease (CVD), cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure and all-cause mortality. This review highlights current CAN epidemiology trends, novel mechanisms linking CAN with other diabetes complications and current recommendations for diagnosis and management of the disease in the clinical setting.

Surgery Residents' Experiences With Seriously-Ill and Dying Patients: An Opportunity to Improve Palliative and End-of-Life Care.

OBJECTIVE: To describe how and when surgery residents provided primary palliative care and engaged specialty palliative care services. DESIGN: Phase I consisted of a previously validated survey instrument supplemented with additional questions. We then conducted semistructured interviews with a subset of the survey respondents (Phase II). Using thematic analysis, we characterized surgery residents' perceptions of palliative care delivery among surgical patients. SETTING: General surgery residency programs across the state of Michigan. PARTICIPANTS: General surgery residents across the state of Michigan. All residents in participating programs were invited to complete the survey in Phase I. Phase II consisted of a subset of the survey respondents who underwent semistructured interviews. Interview respondents were sampled to reflect the overall surveyed group. RESULTS: Among 119 survey respondents (response rate 70%), all had encountered a palliative care specialist but only 58.8% had been taught when to consult or to refer to palliative care. Survey respondents reported on a multitude of barriers within the clinician, patient and family, and systemic domains. Interviews expanded on survey findings and 4 influential factors of palliative care delivery emerged: (1) Resident Education and Training; (2) Resident Attitudes Toward Palliative Care; (3) Knowledge of Palliative Care; and (4) Training within a Surgical Culture. CONCLUSIONS: This study reveals how surgery resident training and experiences impact palliative and end-of-life care for surgical patients at teaching institutions. Knowledge of how and when residents are providing primary palliative care and engaging with palliative care services will inform future knowledge and behavioral interventions for trainees who often provide care for patients nearing the end of life.

Surgeon Perspectives Regarding Death and Dying.

BACKGROUND: Surgical patients most commonly receive palliative care services within 24-48 hours of death, and reasons for this delay are poorly understood. Research with nonsurgeons suggests that physician characteristics and beliefs about death and dying may contribute to late referral. OBJECTIVE: To describe surgeon perspectives related to death and dying, and their relationship with delayed referrals to palliative care. DESIGN: Using a previously validated survey instrument supplemented by open-ended questions, deductive content analysis was used to describe surgeon preferences for end-of-life care. SETTINGS: Participants were all current nonretired members of the American Society of Colon and Rectal Surgeons. MAIN OUTCOME MEASURES: Surgeon descriptions of a "good death" and how personal experiences influence care provided. RESULTS: Among 131 survey respondents (response rate 16.5%), 117 (89.3%) completed all or part of the qualitative portion of the survey. Respondents consistently reported their personal preferences for end-of-life care, and four central themes emerged: (1) pain and symptom management, (2) clear decision making, (3) avoidance of medical care, and (4) completion. Surgeons also reflected on both good and bad experiences with patients and family members dying, and how these experiences impact practice. LIMITATIONS: The small sample size inherent to Internet surveys may limit generalizability and contribute to selection bias. CONCLUSION: This study reveals surgeon preferences for end-of-life care, which may inform initiatives aimed at surgeons who may underuse or delay palliative care services. Future studies are needed to better understand how surgeon preferences may directly impact treatment recommendations for their patients.