Home / Resources / Featured Writers / High-carbohydrate diets may cause accentuation of hyperglycemia

High-carbohydrate diets may cause accentuation of hyperglycemia

Apr 23, 2002

In 1986 the ADA released nutrition guidelines advocating a low-fat diet rich in carbohydrates (up to sixty percent of total energy). In dyslipidemic patients with type 2 diabetes the higher increase in dietary carbohydrates and restriction of fats was advised 55 . Soon after, The National Institutes of Health Consensus Development Conference on Diet and Exercise expressed concerns about recommending high-carbohydrate diets because of their potential harmful raising of triglycerides and lowering of HDL 127

Numerous studies have since challenged the contention that a high-carbohydrate diet improves glycemic control and insulin sensitivity in type 2 diabetes 6, 128-143 . Many demonstrate that high-carbohydrate diets may cause accentuation of hyperglycemia and adversely affect lipoproteins in type 2 diabetes. 142 144, 145 146 147 Garg performed a meta-analysis of several such studies showing that high MUFA diets improve lipoprotein profiles and glycemic control without adverse effects 6 .


In a six week crossover study, Krauss and Dreon 148 149 demonstrated that with a high carbohydrate, low-fat (24%) diet approximately forty percent of patients with a normal lipid profile (pattern A) shifted to the high risk pattern B with small, dense, more atherogenic LDL. Interestingly the majority of patients initially diagnosed with pattern B were already following a high carbohydrate, low-fat diet. This study also shows that a high carbohydrate, low-fat diet raises triglycerides and lowers HDL thereby increasing cardiac risk in patients with normal or abnormal lipid profiles. Furthermore, the researchers were surprised that a high fat (46%), mostly MUFA diet improved triglycerides (TG) in both groups A and B.

Yost et al studied 25 healthy, normal weight subjects to determine the effects of macronutrient composition on fasting and postprandial activities of adipose tissue lipoprotein lipase (LPL) and skeletal muscle LPL on insulin sensitivity152 . In a randomized crossover fashion the subjects ate either a high carbohydrate (55% carbohydrate, 25% fat, and 20% protein) or high fat (30% carbohydrate, 50% fat, 20% protein). The results of the LPL skeletal muscle biopsies and euglycemic clamp determinations of insulin sensitivity suggest that in normal-weight subjects habitual dietary carbohydrate intake may have a stronger effect on subcutaneous fat storage than does dietary fat intake.

In a study specifically designed to test the hypothesis of popular anti-fat advocates, Knopp et al followed 444 men with hypercholesterolemia or mixed hyperlipidemia for one year 150 . They were divided into four dietary groups with fat contents between 30 and 18 percent. Further fat restriction below 26 percent was without benefit, counterproductive, and associated with lowering of HDL and raising triglycerides. Gaziano et al demonstrated that fasting triglycerides may be a powerful independent predictor of coronary heart disease especially when considered in the context of HDL levels, and this has also been supported by others. 124

Hu et al prospectively studied over 80,000 women and found that total fat intake is not significantly is not significantly related to the risk of CHD as long as caloric needs are not exceeded 151 . Rather, it is the type of fat that is important. These Harvard researchers suggest that replacing saturated and trans unsaturated fats with MUFA and PUFA is far more important in preventing heart disease in women than reducing overall fat intake. After reviewing the evidence the American Heart Association recently issued a warning against very low fat diets (< 15% total calories) especially in young children, pregnant women, the elderly, and persons with eating disorders, diabetes, elevated TG levels, and carbohydrate malabsorption illnesses 152 .

The Diet and Reinfarction Trial (DART) 153 and the Lyon Heart Trial 157 achieved striking reductions in CHD and all-cause mortality rates in patients who had already suffered a myocardial infarction. This was achieved by providing n-3 fatty acids and endothelial-protective natural antioxidants from monounsaturated fat sources (nuts and olive oil), fruits, and vegetables. In obese patients and those with mild type 2 diabetes Markovic et al 154, 155 were able to improve insulin action and glycemic control, reduce VLDL and TGs, and increase LDL size by instituting a calorie restricted diet dietary regimen with a macronutrient ratio 38% carbohydrate, 33% protein, and 29% fat. Beneficial effects occurred by day four, and reduced carbohydrate intake was strongly related to the early fall (d4) in glycemia with the reduction of fat in the control group independently having the reverse association. The researchers demonstrated an independent effect of dietary fat on glycemia which they speculate is due to dietary fat slowing the carbohydrate absorption 154 . Further benefits occurred through day 28. Also studying type 2 diabetics while using a diet with a similar calorie restriction and macronutrient ratio with added GLA and fish oil supplements, Sears et al demonstrated significant reductions in fasting insulin levels, glycemia, and lipid profile 156 .

Do We Need to Restrict Protein?

The centuries-old debate among nutritionists regarding dietary protein needs rages on. One needs to consider gender and activity level which could dictate protein requirements up to 1.8 g/kg for those involved in heavy strength exercise. 157 The 100 year-old recommendation of prescribing low or inadequate protein consumption due to fear of exacerbating renal pathology lacks convincing data to support it 158, 159 , and could lead to protein malnutrition 160, 161 . In patients with type 1 diabetes Riley and Dwyer 162 were surprised by a decreased prevalence of microalbuminuria at relatively high intakes of dietary protein.

The endothelial dysfunction model explains how diabetes is associated with renal endothelial injury that allows leakage of protein into the urine 163-165 . Lowering or raising the total dietary protein intake will result in less or more available protein respectively to leak through the injured sites and become detectable in urine. Ingesting adequate amounts of low fat protein along with appropriate types and amounts of carbohydrates and fats will help repair the endothelium and reduce microalbuminuria.

Sears et al 156 have observed an improvement in microalbuminuria in patients with type 2 diabetes after following a hypocaloric diet with the approximate macronutrient ratios described by Markovic but with added GLA and omega-3 supplementation as described by Sears et al 156 . At first Markovic’s protein prescription may seem excessive. But, because the total caloric intake is relatively low 154, 155, 166 , the approximately 30 percent of calories from protein is actually the same or less in quantity than the protein in other diets such as the one recommended by the American Diabetes Association. 166

Lowering protein intake increases the consumption of carbohydrate and fat. Balance is the key.

Modulation of Eicosanoids

Modulation of eicosanoids is possible by controlling delta 6 and delta 5 desaturases through both dietary intake and supplementary GLA and n-3 fatty acids 73, 167-169 .

Ingesting GLA can overcome factors that decrease the normal delta 6 desaturase, bypassing it to be converted to DGLA 167, 170 . Ensuring adequate levels of GLA alone does not ensure desirable eicosanoid balance. Overproduction of DGLA can lead to both an overabundance of PGE1 171 as well as AA-derived inflammatory and vasoconstricting eicosanoids 168 . Their balance depends on controlling delta 5 desaturase, which is activated by insulin and inhibited by glucagon 172 173, 174 . The ratio of protein to carbohydrate consumed at each meal determines the postprandial release and balance of insulin and glucagon 175 . This effect persists for four to six hours.

An important dietary strategy for eicosanoid modulation is to regulate delta 5 desaturase by the appropriate amount and types of macronutrients 156, 176 . The ingestion of the n-3 fatty acid eicosapentaenoic acid (EPA), either from dietary marine sources or supplementary fish oil, competitively inhibits delta 5 desaturase and the subsequent formation of arachidonic acid (AA) and its metabolites 177, 178 .

Combining supplementary GLA with EPA allows one to determine a more favorable of PGE1 series eicosanoids versus the arachidonic acid derived cyclooxygenase and lipoxygenase pathway products 167 . Increased lipoxygenase activity may be associated with increased oxidation of LDL and atherosclerosis. 179

AA is formed by the breakdown of fatty acids, which is catalyzed by phospholipase A2 180 . Isoforms of this enzyme are expressed in beta cells perhaps indicating a further role for AA in insulin secretion 181 . A high intake of AA results in elevated plasma AA levels which may increase AA-derived eicosanoids such as thromboxane A2 72 .

Next time we will examine current dietary trends and programs.

Eric S. Freedland, MD graduated from University of Rochester School of Medicine in 1982, trained in internal medicine at Mt. Auburn Hospital in Cambridge, MA, and emergency medicine at Harbor-UCLA Medical Center in Torrance, CA, and has held faculty positions at Harvard Medical School (1990-1991) and Boston University School of Medicine (1992-1997). Dr. Freedland has developed a nutrition-centered model of disease with a special emphasis on diabetes. A staunch advocate for prescribing lifestyle changes before drugs, Dr. Freedland has written and lectured extensively on this subject.

127. Health NIo. Consensus development conference on diet and exercise in non-insulin-dependent diabetes mellitus. Diabetes Care 1987; 10:639-44.

128. Berry EE, Shlomo; Friedlander, Yechiel; Harats, Dror; Kaufmann, Nathan; Norman, Yehudit; Stein, Yechezkial. Effects of diets rich in monounsaturated fatty acids on plasma lipoporoteins – The Jerusalem Nutrition Study II – Monounsaturated fatty acids vs Carbohydrates. American Journal of Clinical Nutrition 1992; 56:394-403.

129. Bonanome A, Visona A, Lusiani L, et al. Carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus : effects of a low-fat, high carbohydrate diet vs. a diet high in monounsaturated fat. American Journal of Clinical Nutrition 1991; 54:586-590.

130. Campbell L, Marmot P, Dyer J, Borkman M, Storlien L. The High-Monounsaturated Fat Diet as a Practical Alternative or NIDDM. Diabetes Care 1994; 17:177-182.

131. Garg A, Bonanome A, Grundy S, Zhang Z, Unger R. Comparison of a high carbohydrate diet with a high-monounsaturated-fat diet in patients with non-insulin-dependent diabetes mellitus. The New England Journal of Medicine 1988; 319:829-834.

132. Garg A. High-Monounsaturated Fat Diet for Diabetic Patients. Diabetes Care 1994; 17:242-246.

133. Ginsberg HNB, Susan L.; Gilbert, Ame; Karmally, Wahida; Deckelbaum, Richard; Kaplan, Karen; Ramakrishnan, Rajasekhar; Holleran, Steve; Dell, Ralph B. Reduction of plasma cholesterol levels in normal men on an American Heart Association Step 1 diet with added monounsaturated fat. The New England journal of medicine; 322:574-579.

134. Grundy SM. Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cholesterol. New England Journal of Medicine; 314:745-748.

135. Grundy SF, Lea; Nix, Dana; Whelan, Marjorie. Comparison of monounsaturated fatty acids and carbohydrates for reducing raised levels of plasma cholesterol in man. American JOurnal of Clinical Nutrition 1988; 47:965-960.

136. Grundy S. What is the desirable ratio of saturated, polyunsaturated, and monounsaturated faty acids in the diet? American Journal of Clinical Nutrition 1997; 66:988s-990s.

137. Gumbiner B, Low D, Reaven P. Effects of a monounsaturated fatty acid-enriched hypocaloric diet on cardiovascular risk factors in obese patients with type 2 diabetes. Diabetes Care 1998; 21:9-15.

138. Gustafsson I-BV, Bengt; Ohrvall, Margareta;Nydahl, Margaretha. A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects. American Journal of Clinical Nutrition 1994; 59:667-674.

139. Lerman-Garber. Effect of a high-monounsaturated fat diet enriched with avocado in NIDDM patients. Diabetes Care 1994:311-315.

140. Mensink R. Effect of Monounsaturated Fatty Acids Versus Complex Carbohydrates on High-Density Lipoproteins in Healthy Men and Women. The Lancet 1987; January 17, 1987:122-125.

141. Garg AG, Scott M.; Unger, Roger H. Comparison of effects of high and low carbohydrate diets on plasma lipoproteins and insulin sensitivity in patients with mild NIDDM. Diabetes 1992; 41:1278-1289.

142. Chen YDIC, Ann; Zhou, Ming-Yue; Hollenbeck, Claire; Reaven, Gerald. Why do low-fat high-carbohydrate diets accentuate postprandial lipemia in patients with NIDDM? Diabetes Care 1995; 18:10-16.

143. Rasmussen O, Thomsen C, Hansen K, Vesterlund M, Winther E, Kjeld H. Effects on blood pressure, glucose, and lipid levels of a high-monosuaturated fat diet compared with a high-carbohydrate diet in NIDDM subjects. Diabetes Care 1993; 16:1565-1571.

144. Coulston AH, Claire; Swislocki, Arthur; Chen, Y-D. Ida; Reaven, Gerald. Deleterious Metabolic Effects of High Carbohydrate, Sucrose Containing Diets in Patients with Non-Insulin Dependent Diabetes Mellitus. American Journal of Medicine 1987; 82:213-220.

145. Coulston A, Hollenbeck C, Swislocki A, Reaven G. Persistence of Hypertrygliceridemic Effect of Low-Fat High-Carbohydrate Diets in NIDDM Patients. Diabetes Care 1989; 12:94-101.

146. Garg A, Grundy S, Koffler M. Effect of high carbohydrate intake on hyperglycemia, islet function, and plasma lipoporteins in NIDDM. Diabetes Care 1992; 15:1572-1580.

147. McLaughlin T, Abbasi F, Lamendola C, Yeni-Komshian H, Reaven G. Carbohydrate-induced hypertriglyceridemia: an insight into the link between plasma insulin and triglyceride concentrations. J Clin Endocrinol Metab 2000; 85:3085-8.

148. Krauss R, Dreon D. Low-density-lipoprotein subclasses and response to a low-fat diet in healthy men. American Journal of Clinical Nutrition 1995; 62:478s-487s.

149. Dreon DF, Harriet; Miller, Bonnie; Krauss, Ronald. Low density lipoprotein subclass patterns and lipoprotein response to a reduced fat diet in men. The FASEB Journal 1994; 8:121-126.

150. Knopp R, Walden C, Retzlaff M, et al. Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic: the dietary alternatives study. JAMA 1997; 278:1509-1515.

151. Hu F, Stampfer M, Manson J, et al. Dietary fat intake and the risk of coronary heart disease in women. New Engl J Med 1997; 337:1491-9.

152. Lichtenstein A, Van Horn L. Very low fat diets. Circulation 1998; 98:935-939.

153. Burr M, Fehily A, Gilbert J, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989; 2:757-761.

154. Markovic T, Jenkins A, Campbell L, Furler S, Kraegen E, Chisholm D. The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM. Diabetes Care 1998; 21:687-694.

155. Markovic T, Campbell L, Balasubramanian S, et al. Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes. Diabetes Care 1998; 21:695-700.

156. Sears B, Kahl P, Rapier G. A nutrition intervention program to improve glycemia, lipid profiles, and hyperinsulinemia in patients with type 2 diabetes. Diabetes 1998; 47 (suppl 1):A312.

157. Lemon PW. Beyond the zone: protein needs of active individuals. J Am Coll Nutr 2000; 19:513S-521S.

158. Wingen A, Fabian-Bach C, Schaefer F, Mehls O. Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood. Lancet 1997; 19:1117-23.

159. Anderson J, Blake J, Turner J, Smith B. Effects of soy protein on renal function and proteinuria in patients with type 2 diabetes. Am J Clin Nutr 1998; 68 (suppl):1347S-53S.

160. Fouque D. Commentary: meta-analysis. Dietary protein restriction delays the progression of renal disease. Am Coll Physicinas Club 1996; July/august:18.

161. Brodsky I. Effects of low-protein diets on protein metabolism in insulin-dependent diabetes mellitus patients with early nephropathy. J Clin Endocrinol Metab 1992; 75:351-7.

162. Riley M, Dwyer T. Microalbuminuria is positively associated with usual dietary saturated fat intake and negatively associated with usual dietary protein intake in people with insulin-dependent diabetes mellitus. Am J Clin Nutr 1998; 67:50-7.

163. Stehouwer C, Lambert J, Donker A, van Hinsbergh V. Endothelial dysfunction and pathogenesis of diabetic angiopathy. Cardiovasc Res 1997; 34:55-68.

164. Smulders YR, Melina; Stehouwer, Coen; Weijers, Rob; Slaats, Ed; Silberbusch, Edward. Determinants of Progression of Microalbuminuria in Patients With NIDDM. Diabetes Care 1997; 20:999-1005.

165. Stehouwer CDAN, J.J.P.; Zeldenrust; G.C.; Hackeng, W.H.L.; Donker, A.J.M.; Den Ottlander, G.J.H. Urinary albumin excretion, cardiovascular disease , and endothelial dysfunction in non-insulin-dependent diabetes mellitus. The Lancet 1992; 340:319-323.

166. Association JotAD. Nutrition recommendations and principles for people with diabetes mellitus. Journal of the American Dietetic Association 1994; 94:504-506.

167. Horrobin D. Essential Fatty Acids in the Management of Impaired Nerve Function in Diabetes. Diabetes 1997; 46:s90-s93.

168. Huang Y-SM, David; Cantrill, Richard; Poisson, Jean-Pierre. In Vivo and In Vitro Metabolism of Linoleic and y-Linoleic Acids:84-105.

169. Dines KCC, M.A.; Cameron, N.E. Contrasting effects of treatment with @-3 and @-6 essential fatty acids on peripheral nerve function and capillarization in streptozotocin-diabetic ratsn. Diabetologia 1993; 36:1132-1138.

170. Keen H, Payan J, Allawi J, et al. Treatment of diabetic neuropathy with gamma-linolenic acid. Diabetes Care 1993; 16:8-15.

171. Cameron NC, Mary. Metabolic and Vascular Factors in the Pathogenesis of Diabetic Neuropathy. Diabetes 1997; 46:s31-s37.

172. Medeiros L, Liu Y, Chang P, Smith A. Insulin, but not estrogen, correlated with indexes of desaturase function in obese women. Horm Metab Res 1995; 27:235-8.

173. Brenner R. Nutritional and hormonal factors influencing desaturation of essential fatty acids. Prog Lipid Res 1982; 20:41-47.

174. Bezard J, Blond J, Bernard A, Clouet P. The metabolism and availability of essential fatty acids in animal and human tissues. Reprod Nutr Dev 1994; 34:539-68.

175. Westphal S, Gannon M, Nuttall F. Metabolic response to glucose ingested with various amounts of protein. American Journal of Clinical Nutrition 1990; 52:267-272.

176. Sears B. Essential Fatty Acids and Dietary Endocrinology: A Hypothesis for Cardiovascular Treatment. Journal of Advancement in Medicine 1993; 6:211-224.

177. Knapp H, Reilly I, Alessandrini P, FitzGerald G. In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis. N Engl J Med 1986; 314:937-42.

178. Kromhout D, Bosschieter E, Coulander CdL. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985; 312:1205-209.

179. Upston JM, Neuzil J, Witting PK, Alleva R, Stocker R. Oxidation of free fatty acids in low density lipoprotein by 15-lipoxygenase stimulates nonenzymic, alpha-tocopherol-mediated peroxidation of cholesteryl esters. J Biol Chem 1997; 272:30067-74.

180. Vane JA, Erik; Botting Regina. Regulatory functions of the vascular endothelium. The New England Journal Of Medicine 1990; 323:27-36.

181. Jones P, Persaud S. Arachidonic acid as a second messenger in glucose-induced insulin secretion from pancreatic B-cells. J Endocrinology 1993; 137:7-14.