bumin) between the arterial blood pressure (systolic and ... Diet on Plasma Lipoproteins and Apolipoproteins ... have recommended diets for type II (non-insu-.
SHORT REPORTS
according to the criteria of the World Health Organization.
ACKNOWLEDGMENTS
This study received financial support from the Foundation for Medical Research in Region III, Denmark. We appreciate the valuable technical assistance of Tove Enggaard Dorph-Jensen and Marianne Andersen.
DISCUSSION REFERENCES
e studied the urinary excretion of albumin and RBP in 110 IDDM patients with serum creatinine values in the range of 46-1263 fxM (median 85 (xM). There was a weak but statistically significant correlation (particularly with albumin) between the arterial blood pressure (systolic and diastolic) and the urinary excretion (logarithm proteincreatinine ratio) of both proteins (Figs. 1 and 2). The weak correlation between the degree of albuminuriaLMW proteinuria and the height of the arterial blood pressure suggests that factors other than incipient nephropathy may be of importance for the development of arterial hypertension in IDDM patients. Whether the rise in arterial blood pressure is secondary to development of incipient nephropathy or whether that rise per se affects kidney function, thereby causing microproteinuria, is unknown. The second possibility, however, finds no support in a longitudinal study by Mathiesen et al. (2) in which the blood pressure of patients who progressed to incipient nephropathy was not different from those who did not.
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From the Department of Clinical Chemistry, Central Hospital Nykebing Falster, Nykobing Falster, Denmark. Address correspondence and reprint requests to Professor jan Holm, MD, PhD, Institute of Medical Biology, Department of Clinical Chemistry, University of Troms0, Box 977, Troms0 9001, Norway.
1. Wiseman M, Viberti G, Mackintosh D, Jarret RJ, Keen H: Glycaemia, arterial pressure and microalbuminuria in type I (insulin-dependent) diabetes mellitus. Diabetologia 2 6 : 4 0 1 405, 1984 2. Mathiesen ER, Oxenb0ll B, Johansen K, Svendsen PAA, Deckert T: Incipient nephropathy in type I (insulin-dependent) diabetes. Diabetologia 26:406-10, 1984 3. Parving H, Hommel E, Mathiesen E, Sk0tt P, Edsberg M, Bahnsen M, Lauritzen M, Hougaard P, Lauritzen E: Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin-dependent diabetes. Br Med j 296:156-60, 1988 4. Rowe DJF, Anthony F, Polak A, Shaw K, Ward CD, Watts GF: Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus. Ann Clin Biochem 24:477-82, 1987 5. Holm J, Hemmingsen L, Nielsen NV: Relationship between the urinary excretion of albumin and retinol-binding protein in insulin-dependent diabetics. Clin Chim Acta 177:101106, 1988 6. Ratcliffe PJ, Esnouf MP, Ledingham JGG: Tubular reabsorption rates for myoglobin in the isolated perfused rat kidney. Clin Sci 70:595-99, 1986 7. Sumpio BE, Maack T: Kinetics, competition and selectivity of tubular absorption of proteins. Am j Physiol 243:F37992, 1982 8. Emery C, Young RM, Morgan DB, Hay A W M , Tete-Donker D, Rubython J: Tubular damage in patients with hypokalaemia. Clin Chim Acta 140:231-38, 1984
Effects of Changing Amount of Carbohydrate in Diet on Plasma Lipoproteins and Apolipoproteins in Type II Diabetic Patients Eight type II (non-insulin-dependent) normolipidemic diabetic patients (aged 45 ± 15 yr, body mass index 22 ± 2 kg/m 2 , means ± SD) treated with diet alone or diet plus oral hypoglycemic agents were given, in random order for periods of 15 days, two diets with different carbohydrate (CHO) (40 vs. 60% of total calories) and fat (20 vs. 40%) levels. Simple C H O , fiber, saturated fat, cholesterol, and polyunsaturated-saturated fat ratio were similar in the two diets. Total plasma cholesterol was not significantly affected by dietary changes; conversely, plasma triglyceride (1.38 ± 0.59 vs. 1.11 ± 0.39 m M , P < 0.05) and apolipoprotein Cll
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Angela A. Rivellese, MD Rosalba Ciacco, MD Salvatore Cenovese, MD Lidia Patti, BSc Gennaro Marotta, MD Delia Pacioni, RD Giovanni Annuzzi, MD Gabriele Riccardi, MD
(3.8 ± 1 . 4 vs, 3.3 ± 0.8 mg/dl) increased significantly after the high-CHO low-fat diet. Among the various lipoproteins, very-low-density lipoprotein (VLDL) was the most affected by diet: VLDL cholesterol concentrations increased from 0.30 ± 0.19 to 0.43 ± 0.28 m M (P < 0.05), and triglyceride concentrations increased from 0.62 ± 0.33 to 0.88 ± 0.53 m M (P < 0.05). In conclusion, increasing the amount of complex C H O in the diet induces an elevation of VLDL in normolipidemic, nonobese, mildly type II diabetic patients. Diabetes Care 13:446-48, 1990
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SHORT REPORTS
uring past years, national diabetes associations have recommended diets for type II (non-insulin-dependent) diabetic patients in which the amount of complex carbohydrate (CHO) was substantially increased (1,2); the rationale was to reduce the amount of dietary saturated fat, which has a strong influence on plasma cholesterol levels in diabetic patients (3). This enthusiasm for high-complex-CHO diets is not shared unanimously among diabetologists on the basis of the possible deleterious effects of these diets (46). However, the fact that low-fat high-CHO diets may have some deleterious effects on plasma lipoproteins does not imply that the intake of saturated fat should not be decreased. In fact, saturated fat could be substituted also by unsaturated fat, thus leaving the amount of CHO low. Against this background, two alternative approaches (high complex CHO vs. high unsaturated fat) to the dietary treatment of type II diabetic patients can be reasonably proposed. Therefore, we have undertaken this study to compare the effects of these two dietary approaches on plasma lipoproteins and apolipoproteins in nonobese normolipidemic type II diabetic patients who are reasonably well controlled with diet alone or diet plus oral hypoglycemic agents.
D
TABLE 1 Plasma lipid and apolipoprotein (apo) concentrations at end of two dietary periods High-monounsaturatedfat diet Cholesterol (mM) Triglyceride (mM) ApoB (mg/dl) ApoCI (mg/dl) ApoCII (mg/dl) ApoCIII (mg/dl) ApoE (mg/dl)
5.05 1.11 92.6 6.9 3.3 6.7 2.5
± ± ± ± ± ± ±
0.90 0.40 23.4 1.4 0.8 1.9 0.3
High-complexcarbohydrate diet 4.93 1.39 85.5 7.5 3.8 7.4 2.7
± it i; it it it ±
0.93 0.59* 20.1 1.7 1.4* 2.8 0.6
Values are means ± SD. *P < 0.05.
(Boehringer Mannheim) on total serum and lipoprotein fractions. Results are means ± SD. The differences between the two diets were analyzed by Student's paired t test (10). The level of significance was 5% (two-tailed test).
RESULTS RESEARCH DESIGN AND METHODS Eight patients with type II diabetes mellitus participated in the study after giving their informed consent (7). Their age was 45 ± 15 yr (means ± SD), body mass index (BMI) was 22 ± 2 kg/m2, and duration of diabetes was 5 ± 3 yr. Four patients were treated with diet alone, and four were treated with diet plus oral hypoglycemic drugs (dosage and time of administration were kept constant throughout the study). Patients were given two isoenergetic mixed-food diets according to a randomized crossover design. Both diets were low in saturated fat and differed only in that a part of complex CHO of the high-CHO diet (represented mainly by white bread) was substituted by monounsaturated fatty acids (olive oil) in the other diet. Polyunsaturated-saturated fat ratio, cholesterol, monodisaccharides, fiber, and proteins were similar in the two diets. At the end of each dietary period (15 days), a blood sample was drawn in the morning after a 12-h fast for the determination of glucose (glucose oxidase peroxidase; Boehringer Mannheim, Mannheim, FRG), lipoprotein lipid, and apolipoprotein (apo) B, Cl, CM, Clll, and E concentrations (8). Blood glucose was also measured before and 2 h after lunch and before dinner. Lipoproteins were separated by ultracentrifugation (Beckman L5-65) with a fixed-angle rotor combined with a precipitation method (9): very-low-density lipoprotein (VLDL), for 16 h at 40,000 rpm and 16 C; high-density lipoprotein (HDL), by precipitation of LDL; HDL3, for 48 h at 40,000 rpm and 16 C; HDL2, difference between total HDL and HDL3 concentrations. Cholesterol and triglyceride concentrations were analyzed by commercially available enzymatic methods
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No difference was observed in body weight at the end of the two dietary periods. Overall, blood glucose control did not change after the two diets; average daily blood glucose (mean of the 4 samples) was 10.5 ± 1.33 mM after the high-CHO diet and 9.66 ± 1.21 mM after the high-fat diet. The effects of the two diets on plasma lipids and apolipoproteins are shown in Table 1. The high-CHO diet induced a significant increase of plasma triglyceride ( + 22%) and apoCII ( + 15%) without major effects on plasma cholesterol and other plasma apolipoproteins. Among the various lipoproteins, VLDL was the most affected by the two dietary regimens, with an increase of 43% for triglyceride and 70% for cholesterol concentrations after the high-CHO diet (Table 2). All other lipoproteins, i.e., LDL, HDL2/ and HDL3, were similar in lipid concentration after the two dietary periods. DISCUSSION
T
he effects of a high-CHO diet on plasma lipoproteins in type II diabetic patients are still controversial. Most of the studies were aimed at evaluating the effects of dietary measures undertaken in the usual clinical situation. Under those conditions, not only the amount of carbohydrate is changed but also the intake of fiber, saturated fat, protein, and sucrose. All these have proved to be independent effects on lipoprotein metabolism that can interfere with the effect of CHO perse (11). In our study, the two test diets were remarkably similar, the only major difference being the amount of com-
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TABLE 2 Plasma lipoprotein concentrations (mM) at end of two dietary periods
Very-low-density lipoprotein Cholesterol Triglyceride Low-density lipoprotein Cholesterol Triglyceride High-density lipoprotein 2 Cholesterol Triglyceride High-density lipoprotein 3 Cholesterol Triglyceride
Highmonounsaturatedfat diet
High-complexcarbohydrate diet
0.30 ± 0.10 0.61 ± 0.34
0.43 ± 0.27* 0.88 ± 0.52*
3.44 ± 0.88 0.15 ± 0.05
3.10 ± 0.82 0.15 ± 0.04
0.49 ± 0.17 0.09 ± 0.06
0.50 ± 0.19 0.09 ± 0.02
0.65 ± 0.08 0.10 ± 0.02
0.60 ± 0.08 0.11 ± 0.03
Values are means ± SD. *P < 0.05.
plex CHO and monounsaturated fat. Our results clearly indicate that VLDL plasma concentration increases after the high-CHO diet without other significant changes in LDL and HDL concentrations. Previous studies have shown an increase of plasma VLDL triglyceride after a high-CHO diet also in nondiabetic individuals (4). CHO-induced triglyceride elevation is of similar magnitude in our diabetic group and in nondiabetic people. This is probably because our patients were nonobese, normolipidemic, and reasonably well controlled with diet alone or diet plus hypoglycemic agents. In fact, larger elevations of plasma triglyceride have been recorded in individuals with hypertriglyceridemia and/or more severe forms of diabetes (6,12,13). The short-term nature of this study prevents drawing definitive conclusions on the chronic effects of highCHO diets on plasma lipoproteins. Moreover, whether the small increase of VLDL recorded in this study with the high-complex-CHO diet has any major impact on the cardiovascular risk of type II diabetic patients remains to be determined. However, this limited elevation of VLDL induced by dietary CHO can be prevented if CHO and fiber are increased in a parallel fashion in the diabetic diet (14). From the Institute of Internal Medicine and Metabolic Diseases, 2nd Medical School, Naples, Italy. Address correspondence and reprint requests to A.A. Rivellese, Institute of Internal Medicine and Metabolic Diseases, University of Naples, Via S Pansini 5, 80131, Naples, Italy.
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ACKNOWLEDGMENTS
This work was supported in part by the Ministry of Education, University of Naples, Italy. We thank Prof. L.A. Carlson for apolipoprotein measurements performed in King Gustav V Research Institute, Karolinska Hospital, Stockholm.
REFERENCES
1 American Diabetes Association: Nutritional recommendations and principles for individuals with diabetes mellitus: 1986. Diabetes Care 10:126-32, 1987 EASD Nutrition and Diabetes Study Croup: Nutritional recommendations for individuals with diabetes mellitus. Diabetes Nutr Metab 1:145-49, 1988 Abbott WGH, Boyce VL, Grundy SM, Howard BV: Effects of replacing saturated fat with complex carbohydrate in diets of subjects with NIDDM. Diabetes Care 12:102107, 1989 Coulston AM, Liu GC, Reaven GM: Plasma glucose, insulin and lipid responses to high carbohydrate low-fat diets in normal humans. Metabolism 32:52-56, 1983 Coulston AM, Hollenbeck CB, Swislocki ALM, Chen YI, Reaven GM: Deleterious metabolic effects of high carbohydrate, sucrose containing diets in patients with NIDDM. Am I Med 82:213-20, 1987 Garg A, Bonanome A, Grundy SM, Zhang Z, Unger RH: Comparison of a high carbohydrate diet with a high monounsaturated fat diet in patients with non-insulin dependent diabetes mellitus. N Engl j Med 319:829-34, 1988 WHO Expert Committee on Diabetes Mellitus: Second Report. Geneva, World Health Org., 1980 (Tech. Rep. Ser., no. 646) Holmquist L: Quantitation of human serum apolipoprotein B by immunoassay. Clin Chim Ada 121:327-36, 1982 Carlson K: Lipoprotein fractionation. / Clin Pathol 26 (Suppl.):32-37, 1973 10. Snedecor GW, Cochran WG: Statistical Methods. 7th ed. Ames, Iowa State Univ. Press, 1980 11 Riccardi G, Rivellese AA, Mancini M: The use of diet to lower plasma cholesterol levels. Eur Heart I 8 (Suppl. E):79-85, 1987 12. Liu GC, Coulston AM, Reaven GM: Effect of high-carbohydrate low-fat diets on plasma glucose, insulin and lipid responses in hypertriglyceridemic humans. Metabolism 32:750-53, 1983 13. Coulston AM, Hollenbeck CB, Swislocki ALM, Reaven GM: Persistence of hypertriglyceridemic effect of low-fat high-carbohydrate diets in NIDDM patients. Diabetes Care 12:94-101, 1989 14. Rivellese A, Riccardi G, Giacco A, Pacioni D, Genovese S, Mattioli PL, Mancini M: Effect of dietary fibre on glucose control and serum lipoproteins in diabetic patients. Lancet 2:447-50, 1980
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