Kitabchi, Abbas E., MD, PhD
Effects of macronutrients on metabolic parameters in prediabetic women
General Research Subject: Insulin Resistance Pre Diabetes
Focus: Integrated Physiology, Integrated Physiology\Insulin Resistance, Nutrition-Clinical, Obesity, Obesity\Clinical Treatment
Type of Grant: Clinical Translational Research
Project Start Date: July 1, 2012
Project End Date: June 30, 2015
Based on the recent CDC report, more than 70 million Americans have pre-diabetes (IGT) and convert to Type 2 diabetes (T2DM) at the rate of 10% per year if not treated. This conversion of pre-diabetes to diabetes can be delayed by lifestyle modification (LSM), i.e. weight loss and exercise, or medications. However, interruption of these interventions will reverse their benefits.
In our present ADA-supported study, we have investigated the effect of high protein, (HP) vs. high carbohydrate (HC) diets for six months in obese, non-diabetic women where calorie-restricted diets were delivered to these subjects free of charge on a weekly basis. The results demonstrated equal weight loss of 9%-10% in both groups. However, the HC group showed greater oxidative stress and more cardiovascular risk factors (CVR) and other metabolic disorders than the HP diet. Based on these findings, we now propose to investigate the effect of HP and HC diets in a group of prediabetic women and men for six months and compare in the two groups (A) comparative weight loss (B) CVR (C) conversion of IGT to normal glucose tolerance (NGT) or T2DM and (D) markers of oxidative stress. If the HP diet shows greater benefits than the HC diet, it may be more effective and advantageous in preventing T2DM than the HC or medications.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
I am interested to know how various macronutrients, such as high protein or high carbohydrate affect the body’s stress, cardiovascular risk factors in prediabetic subjects. In the last three years, I received a clinical research grant from ADA to study the effects of high protein (30% protein, 30% fat, 40%CHO) or high carbohydrate (55% CHO, 30% fat, 15% protein) on metabolic stress, insulin resistance, cardiovascular risk factors, levels of lipid peroxidation, as well as weight loss in a group of non-diabetic, obese, premenopausal women. These studies showed that if we provided each subject with already prepared foods where they could come to our GCRC and pick up the frozen entrees, and other nutrients in a pre-packaged form on a weekly basis (free of charge) with 500 Kcal reduction calculated for each subject based on their Resting Energy Expenditure both groups lost equal amount of weight, but most importantly, the high protein diet subjects had greater advantage in cardiovascular risk factors, insulin resistance, metabolic stress, and lipid peroxidation than high carbohydrate with similar adherence in both groups in 6 months of follow-up. Therefore, the high protein diet was "less toxic" to the subjects than the high carbohydrate diet.
Based on these findings we hypothesized that a similar protocol studying prediabetic subjects could result in greater advantage for prediabetic subjects with the high protein diet than the high carbohydrate diet. We further hypothesize that high protein diet may convert prediabetes to a non-diabetic state or even prevent conversion of prediabetes to T2DM with a greater rate than the high carbohydrate diet.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
We hope our proposed study in prediabetes gives us some insight as to how to prevent diabetes or even reverse the prediabetic state to non-diabetic, above and beyond the weight loss. If we can show that high protein in prediabetics is "less toxic" than high carbs, we could then look at the same type of protocol with diabetic subjects, which may be proven to be more advantageous to persons with diabetes than high carbohydrate diet. Our previous ADA-supported study showed that both groups of non-diabetic subjects under daily 500 Kcal reduction in diet lost similar amount of weight in 6 months. However, the high protein diet appeared to have more beneficial effects than the standard high carbohydrate diet. Based on these findings we could effectively utilize similar protocols for prediabetics and eventually diabetic individuals.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Since my arrival in Memphis, first as Director of Research at VAMC from 1968-1973, and then as Director of the Division of Endocrinology, Diabetes, and Metabolism at the University of Tennessee Health Science Center (UTHSC) from 1973-2009, I have been involved in numerous studies in diabetes and metabolic-related investigations. These include biological effects of proinsulin, C-peptides, and mechanisms of insulin resistance. From 1976-present, I also conducted numerous prospective, randomized, protocols for various modes of therapy in diabetic ketoacidosis (DKA). These are now the ADA standard protocols for DKA treatment.
I have also been privileged to serve as PI, Co-PI, or principle investigator for three NIDDK-supported studies, and still continue in these studies today:
1. DCCT/EDIC, 2. DPP/DPPOS, 3. Look AHEAD
As you can surmise from the above, I have been involved in diabetes-related studies for more than 40 years, and will probably continue as long as I receive funds and support, and my health permits. I can’t imagine that I can do anything more rewarding than these investigations. I am involved in these studies because helping people with prediabetes and diabetes is rewarding, while I also train young investigators and clinicians during the early part of their training.
In what direction do you see the future of diabetes research going?
With knowledge we have gained in DPP/DPPOS, I feel that prevention is the most important step. We have now more than 70 million subjects with prediabetes (IGT) who will convert to diabetes at a rate of 10% per year if we do not intervene. I hypothesize that not only metabolic interventions, but also with elucidation of roles of various genes we have identified in the DPP/DPPOS studies, we may be able to reduce conversion of IGT to diabetes or even cure diabetes. We have recruited a group of talented and committed, bright people nationally who are able to focus on these problems; but additional funding from various governmental and non-governmental agencies are necessary to achieve our goals which are stated by the American Diabetes Association.
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