Differential caloric restriction and insulin sensitivity impact of valoric bypass surgery versus dietary isnulin in caloric restriction and insulin sensitivity diabetic subjects despite Time-restricted eating habit weight loss. Klein S, Calooric RR Carbohydrate restriction regulates the adaptive response to fasting. Caloric restriction CR has become increasingly attractive in the treatment of type 2 diabetes mellitus T2DM because of the increasingly common high-calorie diet and sedentary lifestyle. Rodriguez R, Moreno M, Lee AY, Godoy-Lugo JA, Nakano D, Nishiyama A, et al.

Caloric restriction and insulin sensitivity -

Diabetes Care 36 7 — Hamman RF, Wing RR, Edelstein SL, Lachin JM, Bray GA, Delahanty L, Hoskin M, Kriska AM, Mayer-Davis EJ, Pi-Sunyer X, Regensteiner J, Venditti B, Wylie-Rosett J Effect of weight loss with lifestyle intervention on risk of diabetes.

Diabetes Care 29 9 — Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG, Son TG, Maudsley S, Carlson OD, Egan JM, Flyvbjerg A, Howell A The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.

Int J Obes 35 5 — Henry RR, Wallace P, Olefsky JM Effects of weight loss on mechanisms of hyperglycemia in obese non-insulin-dependent diabetes mellitus. Diabetes 35 9 — Hui ST, Andres AM, Miller AK, Spann NJ, Potter DW, Post NM, Chen AZ, Sachithanantham S, Jung DY, Kim JK, Davis RA Txnip balances metabolic and growth signaling via PTEN disulfide reduction.

Proc Natl Acad Sci USA 10 — Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, McMahon DJ, Korner J Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell Function in type 2 diabetic patients. Diabetes 62 9 — Jensen MD, Haymond MW, Gerich JE, Cryer PE, Miles JM Lipolysis during fasting.

Decreased suppression by insulin and increased stimulation by epinephrine. J Clin Invest 79 1 — Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, Pearson M, Nassar M, Telljohann R, Maudsley S, Carlson O, John S, Laub DR, Mattson MP Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma.

Free Radic Biol Med 42 5 — Johnson ML, Distelmaier K, Lanza IR, Irving BA, Robinson MM, Konopka AR, Shulman GI, Nair KS Mechanism by which caloric restriction improves insulin sensitivity in sedentary obese adults.

Diabetes 65 1 — Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons M Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus.

J Clin Endocrinol Metab 77 5 — Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction.

Gastroenterology 5 — Klein S, Wolfe RR Carbohydrate restriction regulates the adaptive response to fasting. Am J Phys 5 Pt 1 :E—E CAS Google Scholar. Klempel MC, Kroeger CM, Varady KA Alternate day fasting ADF with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet.

Metabolism 62 1 — Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, Yapp K, Olivan B Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab 93 7 — McCurdy CE, Davidson RT, Cartee GD Calorie restriction increases the ratio of phosphatidylinositol 3-kinase catalytic to regulatory subunits in rat skeletal muscle.

Am J Physiol Endocrinol Metab 5 :E—E Melanson KJ, Summers A, Nguyen V, Brosnahan J, Lowndes J, Angelopoulos TJ, Rippe JM Body composition, dietary composition, and components of metabolic syndrome in overweight and obese adults after a week trial on dietary treatments focused on portion control, energy density, or glycemic index.

Nutr J Omodei D, Fontana L Calorie restriction and prevention of age-associated chronic disease. FEBS Lett 11 — Pereira MA, Jacobs DR Jr, Pins JJ, Raatz SK, Gross MD, Slavin JL, Seaquist ER Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults.

Am J Clin Nutr 75 5 — Schauer PR, Bhatt DL, Kashyap SR Bariatric surgery versus intensive medical therapy for diabetes. N Engl J Med 7 Steven S, Hollingsworth KG, Al-Mrabeh A, Avery L, Aribisala B, Caslake M, Taylor R Very low-calorie diet and 6 months of weight stability in type 2 diabetes: pathophysiological changes in responders and nonresponders.

Diabetes Care 39 5 — Szendroedi J, Yoshimura T, Phielix E, Koliaki C, Marcucci M, Zhang D, Jelenik T, Muller J, Herder C, Nowotny P, Shulman GI, Roden M Role of diacylglycerol activation of PKCtheta in lipid-induced muscle insulin resistance in humans. Proc Natl Acad Sci USA 26 — Trussardi F, Lopes AL, Fernandes PR, Reischak-Oliveira A, Friedman R Impact of weight loss with or without exercise on abdominal fat and insulin resistance in obese individuals: a randomised clinical trial.

Br J Nutr 3 — Varady KA, Bhutani S, Church EC, Klempel MC Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults.

Am J Clin Nutr 90 5 — Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.

Gastroenterology 4 — Xydakis AM, Case CC, Jones PH, Hoogeveen RC, Liu MY, Smith EO, Nelson KW, Ballantyne CM Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction.

J Clin Endocrinol Metab 89 6 — Download references. Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, USA.

You can also search for this author in PubMed Google Scholar. Correspondence to Meera Shah. These findings support the hypothesis that inadequate subcutaneous adipose stores result in lipid overflow into visceral fat and other nonadipose tissues In this regard, visceral fat could be considered as a marker of ectopic fat.

At baseline and at month 6, large fat cells were also the strongest determinant of insulin resistance in these nondiabetic subjects.

This finding prompts speculation that impaired adipogenesis may be the primary defect in insulin resistance, and the hypothesis is supported by findings that humans with partial or complete loss of adipose tissue are extremely insulin resistant 40 , that surgical replacement of adipose stores in the fatless mouse restores insulin sensitivity 41 , and that expression of Wnt signaling genes and adipogenic transcription factors are reduced in nondiabetic subjects with a family history of type 2 diabetes Large fat cells have also been shown to have a different pattern of adipocytokine secretion than smaller fat cells 43 , which may contribute to the strong association between large FCS and insulin sensitivity.

In contrast to previous studies 24 , 26 — 28 , 31 , 44 , 45 , we observed that IMCL was not related to insulin sensitivity. Furthermore, IMCL was not related to adipocyte size. Our results are consistent with the hypothesis that IMCL stores alone are not sufficient to account for impaired insulin action 46 — Liver lipid, on the other hand, was inversely related to insulin sensitivity.

Liver lipid content has previously been reported to correlate with measures of whole-body insulin sensitivity in individuals with and without diabetes 30 , 34 , 35 , 38 , 49 , but this relationship is difficult to explain mechanistically because most ingested or infused glucose is taken up by muscle.

Theoretically, IHL is expected to correlate with reduced hepatic insulin sensitivity impaired insulin suppression of glucose rate of appearance and not necessarily with whole-body insulin action.

However, the accumulation of hepatic triglyceride has been hypothesized to reduce insulin clearance and lead to peripheral insulin resistance via a downregulation of insulin receptors 34 , Clearly, prospective human studies that define whether lipid accumulation in liver precedes insulin resistance would be of interest.

Contrary to some previous studies 51 , 52 , we observed that diet alone or with exercise produced identical reductions in weight, fat mass, and abdominal fat mass. These conflicting results may be due to inaccurate calculations of the energy costs of the prescribed activity in those studies, which would lead to differences in energy deficits among groups.

We also observed that FCS was reduced in response to an energy deficit, but we could not detect an additional effect of exercise. Our study was underpowered to detect differences in FCS among groups and our results contrast with the reports of You et al.

The current study is also the first to simultaneously measure ectopic fat stores in both muscle and liver in response to a calorie restriction intervention. We found that the calorie restriction alone or with exercise did not affect IMCL in the soleus.

These results are consistent with previous studies 6 , 14 , 15 and together with the findings that IMCL was not independently related to S i suggest that IMCL accumulation alone is not likely to be a causal factor leading to acquired insulin-signaling defects in muscle. Many other factors, including lipid droplet size, location of lipid droplets relative to mitochondria, and muscle oxidative capacity, are all potential determinants of insulin resistance 15 , 48 , An alternate hypothesis is that the capacity for lipid metabolism is an important mediator in the association between IMCL and insulin resistance.

Caution must be exercised when interpreting these results because the study may have been underpowered to detect small differences in IHL among groups. The reduction in liver lipid levels is consistent with results of Tiikkainen et al.

In addition, we also observed parallel reductions in IHL and abdominal visceral fat. In summary, calorie restriction by diet alone or in conjunction with exercise leads to similar improvements in insulin sensitivity and reductions in β-cell sensitivity in overweight, glucose-tolerant subjects.

The study also provides support for the hypothesis that the underlying pathologic cause of insulin resistance is related to abnormal partitioning of fat among adipose, hepatic, muscle, and pancreatic tissues, probably as a result of an inability to make new fat cells.

However, the finding that IMCL was not responsive to weight loss despite improvements in insulin sensitivity suggests that intracellular fat accumulation is not a causal factor in insulin resistance in muscle. Overall, this study provides new evidence to suggest that impaired adipogenesis and increased liver lipid infiltration occur early in the pathogenesis of insulin resistance.

In healthy overweight men and women at baseline, there was a strong positive correlation between abdominal subcutaneous FCS and VAT A and abdominal subcutaneous FCS and IHL B. Groups were pooled for analysis. The improvement in insulin sensitivity with 6 months of calorie restriction was significantly associated with the loss of fat mass A and abdominal VAT depots B but not to the change in subcutaneous abdominal FCS C and IHL D.

Analyses are reported with and without the control group included. Physical characteristics of the subject groups at baseline and following 6 months of calorie restriction. Differences between treatment groups for the change scores using an ANCOVA with the absolute change as the dependent variable and the baseline score as a covariate.

This work was supported by grants U01 AG to E. and K01 DK to D. is supported by a Neil Hamilton-Fairley Training Fellowship awarded by the National Health and Medical Research Council of Australia ID The authors thank the remaining members of the Pennington CALERIE Research Team: James DeLany, Corby Martin, Julia Volaufova, Marlene Most, Lilian de Jonge, Tuong Nguyen, Frank Greenway, Emily York-Crow, Catherine Champagne, Brenda Dahmer, Andy Deutsch, Paula Geiselman, Jennifer Howard, Jana Ihrig, Michael Lefevre, Darlene Marquis, Connie Murla, Sabrina Yang, Robbie Durand, Sean Owens, Aimee Stewart, and Vanessa Tarver.

Our gratitude is extended to the excellent staffs of the Inpatient Clinic and Metabolic Kitchen. Our thanks also go to Health and Nutrition Technology Carmel, CA for providing us with all of the HealthOne formula used in the study and to Edward J.

Robarge for technical assistance with collection of the magnetic resonance spectroscopy data. Finally, our profound gratitude goes to all the volunteers who spent so much time participating in this very demanding research study.

is currently affiliated with the Department of Family and Consumer Sciences, University of Wyoming, Laramie, Wyoming. is currently affiliated with the Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.

A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. Section solely to indicate this fact. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.

filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 29, Issue 6. Previous Article Next Article. RESEARCH DESIGN AND METHODS. Article Information. Article Navigation.

Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, β-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects D.

Enette Larson-Meyer, PHD ; D. Enette Larson-Meyer, PHD. This Site. Google Scholar. Leonie K. Heilbronn, PHD ; Leonie K. Heilbronn, PHD. Leanne M. Redman, PHD ; Leanne M. Redman, PHD. Bradley R. Newcomer, PHD ; Bradley R.

Newcomer, PHD. Madlyn I. Frisard, PHD ; Madlyn I. Frisard, PHD. Steve Anton, PHD ; Steve Anton, PHD. Steven R. Smith, MD ; Steven R. Smith, MD. Anthony Alfonso, MAPLSTAT ; Anthony Alfonso, MAPLSTAT. Eric Ravussin, PHD ; Eric Ravussin, PHD.

Insulin sensitivity was assessed using the minimal model analysis of frequently sampled intravenous glucose tolerance tests. Subjects who increased from 1, to 4, kJ to 1, calories had worse fasting glycemic control in spite of continued weight loss, whereas subjects who remained on 4, kJ 1, calories throughout had further improvements in both blood glucose and insulin sensitivity with increased weight loss.

Both degree of calorie restriction and magnitude of weight loss have independent effects on improvements in glycemic control and insulin sensitivity. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.

filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 17, Issue 1. Previous Article Next Article. Article Navigation. Original Articles January 01 Caloric Restriction Per Se Is a Significant Factor in Improvements in Glycemic Control and Insulin Sensitivity During Weight Loss in Obese NIDDM Patients Rena R Wing, PHD ; Rena R Wing, PHD.

Department of Psychiatry, University of Pittsburgh School of Medicine.

Rena R WingAndd H BlairPatricia Bononi caloric restriction and insulin sensitivity, Marsha D MarcusRichard WatanabeRichard N Bergman; Caloric Restriction Per Se Is a Significant Factor in Herbal remedies for menstrual cramps in Caloric restriction and insulin sensitivity Control and Insulib Sensitivity During Weight Loss in Rdstriction NIDDM Patients. Diabetes Care 1 January ; caloric restriction and insulin sensitivity annd : 30— To restrictioj the effects of caloric restriction, independent of differences in weight loss, on improvements in glycemic control, fasting insulin, and insulin sensitivity. Insulin sensitivity was assessed using the minimal model analysis of frequently sampled intravenous glucose tolerance tests. Subjects who increased from 1, to 4, kJ to 1, calories had worse fasting glycemic control in spite of continued weight loss, whereas subjects who remained on 4, kJ 1, calories throughout had further improvements in both blood glucose and insulin sensitivity with increased weight loss. Both degree of calorie restriction and magnitude of weight loss have independent effects on improvements in glycemic control and insulin sensitivity. Sign In or Create an Account.

Video

Calorie Restriction and Controlling the Rate of Aging