Towards Optimal Management of Diabetes in Surgery by Sanjeev Kelkar & Shubhangi Muley & Prakash Ambardekar

Author:Sanjeev Kelkar & Shubhangi Muley & Prakash Ambardekar
Language: eng
Format: epub
ISBN: 9789811377051
Publisher: Springer Singapore

6.14.4 New Agents

Diabetes and heart failure with diabetic cardiomyopathy are now recognized to have a frequent association. A new class of drugs, SGLT2, with a number of related molecules from the same class has emerged that increases glycosuria, induces some weight loss, and produces as a result a mild form of ketonemia. These ketone bodies are then utilized by the heart muscle for its fuel requirement. What was unexpected was the early separation of the Kaplan-Meier graphs in the improvement in cardiac muscle function from within a couple of weeks in the trials which continued to improve over weeks to follow, compared to the other arm. These are considered as useful drugs since a couple of years now.

Hydroxychloroquine is in use for autoimmune disorders like rheumatoid arthritis for decades. Many well-designed trials have now shown its effectiveness in blood glucose control as well lately. The most singular effect observed is the stabilization of insulin dose in fluctuating diabetic patients [20].

Uncontrolled diabetes is considered in addition to hypercoagulable or immunocompromised, and such other associated state is also considered an inflammatory state. Hydroxychloroquine, an immunomodulator and anti-inflammatory drug used in rheumatoid arthritis for decades, has been tried in type 2 diabetes for its anti-inflammatory properties. In a study with small number of patients, the control arm was only insulin, and the intervention arm was insulin with hydroxychloroquine (HCQS.) The treatment arm showed that the insulin requirement was decreased in the intervention arm compared to the control arm [21].

The impact of oral antidiabetic agents on changes in lipid levels, either increasing or decreasing, is an important consideration. The lipid-lowering effect should go beyond the lowering that may be caused by glycemic control alone. Hyperlipidemia and atherosclerosis go together. In a head-to-head trial between pioglitazone and HCQS, reduction in the total cholesterol and LDL, cholesterol was found to be significantly lower in the HCQS rather than pioglitazone group [22]. In addition to its effects on the reduction in LDL-C, lowered insulin requirement and better glycemic control, as a result of its anti-inflammatory properties, HCQS is reported to have an antithrombotic property also. Thus HCQS could provide an added advantage in reducing cardiovascular risk [22].

The possible explanation for the glucose-lowering effect of hydroxychloroquine can be given by a series of reactions occurring in the intracellular realm. The insulin-insulin receptor combination is internalized in the cytosol. The parent drug, chloroquine, stabilizes intracellular lysosomes. That leads to the process of lysosomal insulin-insulin receptor combination degradation slowing down. The parent drug chloroquine slows insulin clearance. The cystosolic insulin-metabolizing enzymes are inhibited by hydroxychloroquine. All these reactions lead to a lowering of glucose with HCQS [23].

A considerable literature is now available about significant vitamin D deficiency in high number of Indians and its benefits in diabetes also when corrected, generally with calcium supplementation. This is not surprising at all since every cellular function that involves exocytosis as in the case of insulin secretion or as in muscle contraction has a concomitant need for exogenous calcium to move in the cells and mobilization of cytosolic calcium for this process to occur.

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