Jagdeesh Ullal

Diabetic neuropathies: clinical manifestations and current treatment options

Diabetic neuropathies are a heterogeneous group of disorders that include a wide range of abnormalities. They can be focal or diffuse, proximal or distal, affecting both peripheral and autonomic nervous systems, causing morbidity with significant impact on the quality of life of the person with diabetes, and can result in early death. Distal symmetric polyneuropathy, the most common form of diabetic neuropathy, usually involves small and large nerve fibers. Small-nerve-fiber neuropathy often presents with pain but without objective signs or electrophysiologic evidence of nerve damage, and is recognized as a component of the impaired glucose tolerance and metabolic syndromes. The greatest risk resulting from small-fiber neuropathy is foot ulceration and subsequent gangrene and amputation. Large-nerve-fiber neuropathies produce numbness, ataxia and uncoordination, impairing activities of daily living and causing falls and fractures. A careful history and detailed physical examination are essential for the diagnosis. Symptomatic therapy has become available and newer and better treatment modalities, based on etiologic factors, are being explored with potential for significant impact on morbidity and mortality. Preventive strategies and patient education still remain key factors in reducing complication rates and mortality.

Comparison of an Electronic Glycemic Management System Versus Provider-Managed Subcutaneous Basal Bolus Insulin Therapy in the Hospital Setting

Background: American Diabetes Association (ADA) guidelines recommend a basal bolus correction insulin regimen as the preferred method of treatment for non–critically ill hospitalized patients. However, achieving ADA glucose targets safely, without hypoglycemia, is challenging. In this study we evaluated the safety and efficacy of basal bolus subcutaneous (SubQ) insulin therapy managed by providers compared to a nurse-directed Electronic Glycemic Management System (eGMS). Method: This retrospective crossover study evaluated 993 non-ICU patients treated with subcutaneous basal bolus insulin therapy managed by a provider compared to an eGMS. Analysis compared therapy outcomes before Glucommander (BGM), during Glucommander (DGM), and after Glucommander (AGM) for all patients. The blood glucose (BG) target was set at 140-180 mg/dL for all groups. The safety of each was evaluated by the following: (1) BG averages, (2) hypoglycemic events <40 and <70 mg/dL, and (3) percentage of BG in target. Result: Percentage of BG in target was BGM 47%, DGM 62%, and AGM 36%. Patients’ BGM BG average was 195 mg/dL, DGM BG average was 169 mg/dL, and AGM BG average was 174 mg/dL. Percentage of hypoglycemic events <70 mg/dL was 2.6% BGM, 1.9% DGM, and 2.8% AGM treatment. Conclusion: Patients using eGMS in the DGM group achieved improved glycemic control with lower incidence of hypoglycemia (<40 mg/dL and <70 mg/dl) compared to both BGM and AGM management with standard treatment. These results suggest that an eGMS can safely maintain glucose control with less hypoglycemia than basal bolus treatment managed by a provider.

Use of a Computer-Based Insulin Infusion Algorithm to Treat Diabetic Ketoacidosis in the Emergency Department

BACKGROUND Efforts at improving quality metrics in diabetes focus on minimizing adverse events and avoiding re-admissions to the hospital. Our experience with Glucommander™ (Glytec, Greenville, SC), a cloud-based insulin management software system, suggested that its use in the emergency department (ED) would be useful in treating patients with mild diabetic ketoacidosis (DKA). MATERIALS AND METHODS Thirty-five patients seen in the ED with hyperglycemic crises and diagnosed with DKA during one calendar year were reviewed. A retrospective chart review was performed on patients who were placed on Glucommander™ for DKA management. We excluded patients with significant acidosis or concomitant medical illnesses. RESULTS Initial average capillary glucose level was 487 ± 68 mg/dL, average time to target glucose was 5 h 11 min, and rate of hypoglycemia (blood glucose level <70 mg/dL) was less than 0.3%. Sixteen patients treated with the protocol were discharged from the ED directly, and 19 were admitted. Patients were maintained for an average of 14 ± 1 h on the Glucommander™ protocol. There was a significantly higher anion gap (P = 0.002) and lower serum bicarbonate level (P = 0.006) in the admitted group. We found very low evidence of re-admission (6%) within 30 days of discharge from the ED for DKA patients. No significant glucose-related adverse events were noted. CONCLUSIONS Use of Glucommander™ for guiding the insulin treatment of mild DKA in the ED can decrease admissions to the hospital for DKA by 45%. Low rates of hypoglycemia make this an option to improve efficiency of utilization of inpatient hospital beds. The cost savings for nonadmissions were estimated at

Improvement in Inpatient Glycemic Care: Pathways to Quality

78,000 over the 12 months of the study. Our results suggest that Glucommander™ is a safe and efficient tool for use in the ED to manage mild to moderate DKA.

Other Therapeutic Agents for the Treatment of Diabetic Neuropathy

The management of inpatient hyperglycemia is a focus of quality improvement projects across many hospital systems while remaining a point of controversy among clinicians. The association of inpatient hyperglycemia with suboptimal hospital outcomes is accepted by clinical care teams; however, the clear benefits of targeting hyperglycemia as a mechanism to improve hospital outcomes remain contentious. Glycemic management is also frequently confused with efforts aimed at intensive glucose control, further adding to the confusion. Nonetheless, several regulatory agencies assign quality rankings based on attaining specified glycemic targets for selected groups of patients (Surgical Care Improvement Project (SCIP) measures). The current paper reviews the data supporting the benefits associated with inpatient glycemic control projects, the components of a successful glycemic control intervention, and utilization of the electronic medical record in implementing an inpatient glycemic control project.

Comparison of Computer-Guided Versus Standard Insulin Infusion Regimens in Patients With Diabetic Ketoacidosis:

The pathogenesis of diabetic neuropathy is complex and it is important to understand the underlying pathology leading to the complication in order to best tailor treatment for each individual patient. It is unlikely that reversing any single mechanism will prove sufficient for reversing nerve damage. Several drugs, such as antioxidant, PKC inhibitors and nerve growth factors can have effects on multiple systems that are compromised in diabetic neuropathy, yet even those may not be enough in and of themselves to completely restore neurological function. Combination therapy may prove to be the best long term approach, and studies of those combinations should prove revealing as to the relative roles of metabolic dysfunction, microvascular insufficiency and autoimmunity in the diabetic neuropathy patient population.

A 70-year-old male with peripheral neuropathy, ataxia and antigliadin antibodies shows improvement in neuropathy, but not ataxia, after intravenous immunoglobulin and gluten-free diet

Background: This study was performed to investigate the efficacy of Glucommander (GM) (Glytec®), a computer-based algorithm versus standard (paper form-based) continuous insulin infusion (CII) in the treatment of patients with diabetic ketoacidosis (DKA). Methods: This was a retrospective multicenter study involving 2665 patients with DKA treated with either GM (n = 1750) or standard protocols (n = 915) across 34 institutions in the United States. GM estimates the rate of CII using an insulin sensitivity factor referred to as a “multiplier” that ranges between 0.01 and 0.03. Outcomes of interest were differences in time to resolve DKA (blood glucose [BG] <200 mg/dL and bicarbonate < 18 mmol/L) and number of hypoglycemic events defined as a BG <70 mg/dl. Results: Treatment with GM was associated with lower rates of hypoglycemia during the time of the insulin drip (12.9% vs 35%, P = .001), faster time to normalization of blood glucose (9.7 ± 8.9 vs 10.97 ± 10.2 hours, P = .0001) and resolution of metabolic acidosis (13.6 ± 11.8 vs 17.3 ± 19.6 hours, P = .0001), and shorter hospital length of stay (3.2 ± 2.9 vs 4.5 ± 4.8 days, P = .01) compared to standard care. Best treatment outcomes were achieved with an initial multiplier of 0.01 and a glucose target range between 120 and 180 mg/dl. Conclusion: The GM algorithm in DKA treatment resulted in lower rates of hypoglycemia and faster DKA resolution over standard paper-based algorithms. Prospective randomized clinical trials comparing the efficacy and cost of computer-based algorithms versus standard CII regimens are warranted.

Antibodies to Neuronal Structures: Innocent bystanders or neurotoxins?

This is a case of a 70-year-old man with severe peripheral neuropathy, type 2 diabetes and progressively worsening cerebellar ataxia. He was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology. The peripheral neuropathy improved with a gluten-free diet, antioxidants and intravenous immunoglobulin, whereas the ataxia did not. This case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia.