humulin-s and Diabetic-Neuropathies

Diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. Although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown.. In the present study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical neurological assessment. Subsequently, 41 non-neuropathic patients, 24 of whom were receiving multiple daily insulin injections (MDII) and 17 receiving continuous subcutaneous insulin infusion (CSII), underwent nerve excitability testing, a technique that assesses axonal ion channel function and membrane potential in human nerves. Treatment groups were matched for glycaemic control, body mass index, disease duration and gender. Neurophysiological parameters were compared between treatment groups and those taken from age and sex-matched normal controls.. Prominent differences in axonal function were noted between MDII-treated and CSII-treated patients. Specifically, MDII patients manifested prominent abnormalities when compared with normal controls in threshold electrotonus (TE) parameters including depolarizing TE(10-20ms), undershoot and hyperpolarizing TE (90-100 ms) (P < 0.05). Additionally, recovery cycle parameters superexcitability and subexcitability were also abnormal (P < 0.05). In contrast, axonal function in CSII-treated patients was within normal limits when compared with age-matched controls. The differences between the groups were noted in cross-sectional analysis and remained at longitudinal follow-up.. Axonal function in type 1 diabetes is maintained within normal limits in patients treated with continuous subcutaneous insulin infusion and not with multiple daily insulin injections. This raises the possibility that CSII therapy may have neuroprotective potential in patients with type 1 diabetes.

Topics: Adult; Axons; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Hypoglycemic Agents; Infusions, Subcutaneous; Insulin; Insulin Infusion Systems; Insulin, Regular, Human; Longitudinal Studies; Male; Neurologic Examination; Neuroprotective Agents; New South Wales; Peripheral Nervous System

Diabetes mellitus (DM), a multifaceted metabolic disorder if not managed properly leads to secondary complications. Diabetic peripheral neuropathy (DPN) is one such complication caused by nerve damage that cannot be reversed but can be delayed. Recently, diabetes patients are using dietary supplements, although there remains a general skepticism about this practice. Curcumin (CUR), one such supplement can help prevent underlying low-grade inflammation in diabetes, but it is plagued by poor oral bioavailability. To better understand the role of bioavailability in clinical outcomes, we have tested double-headed nanosystems containing curcumin (nCUR) on DPN. Because CUR does not influence glucose levels, we have also tested the effects of nCUR combined with long-acting subcutaneous insulin (INS). nCUR with or without INS alleviates DPN at two times lower dose than unformulated CUR, as indicated by qualitative and quantitative analysis of the hind paw, sciatic nerve, spleen, and L4-6 spinal cord. In addition, nCUR and nCUR+INS preserve hind paw nerve axons as evident by the Bielschowsky silver stain and intraepidermal nerve fibers (IENF) density measured by immunofluorescence. The mechanistic studies further corroborated the results, where nCUR or nCUR+INS showed a significant decrease in TUNEL positive cells, mRNA expression of NLRP3, IL-1β, and macrophage infiltration while preserving nestin and NF200 expression in the sciatic nerve. Together, the data confirms that CUR bioavailability is proportional to clinical outcomes and INS alone may not be one of the solutions for DM. This study highlights the potential of nCUR with or without INS in alleviating DPN and warrants further investigation.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Insulin; Insulin, Regular, Human; Rats; Rats, Sprague-Dawley

Hypoglycemic events in patients with type 1 diabetes (T1D) are associated with measurable electroencephalography (EEG) changes. Previous studies have, however, evaluated these changes on a single EEG channel level, whereas multivariate analysis of several EEG channels has been scarcely investigated. The aim of the present work is to use a coherence approach to quantitatively assess how hypoglycemia affects mutual connectivity of different brain areas.. EEG multichannel data were obtained from 19 patients with T1D (58% males; mean age, 55 ± 2.4 years; diabetes duration, 28.5 ± 2.6 years; glycated hemoglobin, 8.0 ± 0.2%) who underwent a hyperinsulinemic-hypoglycemic clamp study. The information partial directed coherence (iPDC) function was computed through multivariate autoregressive models during eu- and hypoglycemia in the theta and alpha bands.. In passing from eu- to hypoglycemia, absolute values of the iPDC function tend to decrease in both bands in all combinations of the considered channels. In particular, the scalar indicator [Formula: see text], which summarizes iPDC information, significantly decreased (P < 0.01) in 17 of 19 subjects: from T5-A1A2 to C3-A1A2 from O1-A1A2 to C4-A1A2 and from O2-A1A2 to Cz-A1A2 in the theta band and from O1-A1A2 to T4-A1A2 and from O1-A1A2 to C4-A1A2 in the alpha band.. The coherence decrease measured by iPDC in passing from eu- to hypoglycemia is likely related to the progressive loss of cognitive function and altered cerebral activity in hypoglycemia. This result encourages further quantitative investigation of EEG changes in hypoglycemia and of how EEG acquisition and real-time processing can support hypoglycemia alert systems.

Topics: Algorithms; Alpha Rhythm; Asymptomatic Diseases; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Electroencephalography; Female; Glucose Clamp Technique; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Insulin, Short-Acting; Male; Middle Aged; Models, Neurological; Recombinant Proteins; Theta Rhythm