Summary
In adults hyperinsulinaemia is associated with an atherogenic risk profile including obesity, low levels of HDL-cholesterol, high levels of triglycerides and elevated blood pressure. To examine these associations in the young we studied the cross-sectional relationships of insulin with obesity indices (body mass index, subscapular skinfold thickness), serum lipids and blood pressure in 1,865 children, adolescents and young adults aged 6–24 years. We also used longitudinal data to study the value of a single insulin measurement to predict high risk factor levels and clustering of multiple risk factors after a 6-year follow-up. In cross-sectional analyses the levels of triglycerides, HDL-cholesterol, systolic blood pressure and obesity indices were usually significantly different across the quartiles of fasting insulin in both sexes among children, adolescents and young adults. In general, no associations were seen with total cholesterol or LDL-cholesterol. In prospective analysis elevated baseline insulin was related to the incidence of hypertriglyceridaemia (≥95th percentile) at the follow-up. This relationship persisted even after adjustments for baseline obesity or 6-year change in obesity status. Moreover, baseline insulin concentration was higher in subjects who subsequently showed clustering of high triglycerides, low HDL-cholesterol and high systolic blood pressure levels at the follow-up. We conclude that high fasting insulin levels measured in children and adolescents predict the development of hypertriglyceridaemia years later. In addition, high insulin levels seem to precede the development of a potentially atherogenic risk factor profile including low HDL-cholesterol, high triglycerides and high systolic blood pressure.
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Abbreviations
- SBP:
-
Systolic blood pressure
- DBP:
-
diastolic blood pressure
- BMI:
-
body mass index
References
Kotchen JM, Kothchen TA, Guthrie GP, Cottrill CM, McKean HE (1980) Correlates of adolescent blood pressure at five-year follow-up. Hypertension 2 [Suppl I]: I-124–I-129
Salonen JT, Puska P, Kottke TE, Heinonen OP (1981) Coronary risk factor clustering patterns in Eastern Finland. Int J Epidemiol 10: 203–210
Criqui MH, Cowan LD, Heiss G, Haskell WL, Laskarzewski PM, Chambless LE (1986) Frequency and clustering of nonlipid coronary risk factors in dyslipoproteinemia. The Lipid Research Clinics Program Prevalence Study. Circulation 73 [Suppl I]: 40–50
Williams RR, Hunt SC, Hopkins PN et al. (1988) Familial dyslipidemic hypertension. Evidence from 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension. JAMA 259: 3579–3586
BØnaa KH, Thelle DS (1991) Association between blood pressure and serum lipids in a population. The TromsØ Study. Circulation 83: 1305–1314
Modan M, Halkin H, Almog S et al. (1985) Hyperinsulinemia: a link between hypertension, obesity and glucose intolerance. J Clin Invest 75: 809–817
Fun M M-T, Shieh S-M, Wu D-A, Chen Y-D I, Reaven GM (1987) Abnormalities of carbohydrate and lipid metabolism in patients with hypertension. Arch Intern Med 147: 1035–1038
Manolio TA, Savage PJ, Burke GI et al. (1990) Association of fasting insulin with blood pressure and lipids in young adults. The CARDIA Study. Arteriosclerosis 10: 430–436
Ferrannini E, Haffner SM, Mitchell BD, Stern MP (1991) Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia 34: 416–422
Kannel WB (1977) Importance of hypertension as a major risk factor in cardiovascular disease. In: Genest J, Koiw E, Kuchel O (eds) Hypertension. McGraw-Hill, New York, pp 888–910
Welborn TA, Wearne K (1979) Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care 2: 154–160
Ducimetiere P, Eschwege E, Papoz L, Richard JL, Claude JR, Rosselin G (1980) Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 19: 205–210
PyörÄlÄ K, Savolainen E, Kaukola S, Haapakoski J (1985) Plasma insulin as coronary risk factor: relationships to other risk factors and predictive value during 9 1/2 year follow-up of the Helsinki Policeman Study population. Acta Med Scand [Suppl] 701: 38–52
Brunner D, Weisport J, Meshular N et al. (1987) Relations of serum total cholesterol and high-density lipoprotein cholesterol percentage to the incidence of definite coronary events: twenty-year follow-up of the Donolo-Tel Aviv Prospective Coronary Artery Disease Study. Am J Cardiol 59: 1271–1276
Abbott RD, Wilson PW, Kannel WB, Castelli WP (1988) High density cholesterol, total cholesterol screening, and myocardial infarction. The Framingham Study. Arteriosclerosis 8: 207–211
Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607
Jarrett RJ (1992) In defence of insulin: a critique of syndrome X. Lancet 340: 469–471
Gidding SS (1993) Relationships between blood pressure and lipids in childhood. Pediatr Clin N Am 40: 41–49
Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP (1992) Prospective analysis of the insulin-resistance syndrome (Syndrome X). Diabetes 41: 715–722
Mitchell BD, Haffner SM, Hazuda HP, Valdez R, Stern MP (1992) The relation between serum insulin levels and 8-year changes in lipid, lipoprotein, and blood pressure levels. Am J Epidemiol 136: 12–22
MykkÄnen L, Kuusisto J, Haffner SM, PyörÄlÄ K, Laakso M (1994) Hyperinsulinemia predicts multiple atherogenic changes in lipoproteins in elderly subjects. Arterioscler Thromb 14: 518–526
MykkÄnen L, Kuusisto J, PyörÄlÄ K, Laakso M (1993) Cardiovascular disease risk factors as predictors of type 2 (non-insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia 36: 553–559
åkerblom HK, Viikari J, Uhari M et al. (1985) Atherosclerosis precursors in Finnish children and adolescents. I. General description of the cross-sectional study of 1980, and an account of the children's and families' state of health. Acta Paediatr Scand [Suppl] 318: 49–63
åkerblom HK, Uhari M, Pesonen E et al. (1991) Cardiovascular Risk in Young Finns. Ann Med 23: 35–39
Owen GM (1982) Measurement, recording, and assessment of skinfold thickness in childhood and adolescence: report of a small meeting. Am J Clin Nutr 35: 629–638
Uhari M, Nuutinen EM, Turtinen J et al. (1991) Blood pressure in children, adolescents and young adults. Ann Med 23: 47–51
Dahlström S, Viikari J, åkerblom HK et al. (1985) Atherosclerosis precursors in Finnish children and adolescents. II. Height, weight, body mass index, and skinfolds, and their correlation to metabolic variables. Acta Paediatr Scand [Suppl] 318: 65–78
Finley PR, Schifman RB, Williams J, Lichti DA (1978) Cholesterol in high density lipoprotein: use of Mg2+/dextran sulphate in its enzymatic measurement. Clin Chem 24: 931–937
Viikari J, åkerblom HK, Nikkari T et al. (1985) Atherosclerosis precursors in Finnish children and adolescents. IV. Serum lipids in newborns, children and adolescents. Acta Paediatr Scand [Suppl] 318: 103–109
Viikari J, Rönnemaa T, SeppÄnen A et al. (1991) Serum lipids and lipoproteins in children, adolescents and young adults in 1980–1986. Ann Med 23: 53–59
Friedewald WT, Levy R, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 18: 499–502
Herbert V, Lau KS, Gottlieb CW, Bleicher SJ (1965) Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab 25: 1375–1384
SAS Institute Inc. (1988) SAS/STAT User's Guide. Release 6.03. SAS Institute Inc., Cary, NC
Hubert HB (1986) The importance of obesity in the development of coronary risk factors and disease: the epidemiologic evidence. Annu Rev Public Health 7: 493–502
KarhapÄÄ P, Voutilainen E, Kovanen PT, Laakso M (1993) Insulin resistance in familial and nonfamilial hypercholesterolemia. Arterioscler Thromb 13: 41–47
Laws A, King AC, Haskell WL, Reaven GM (1991) Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men. Arterioscler Thromb 11: 1636–1642
Lautala P, åkerblom HK, Viikari J et al. (1985) Atherosclerosis precursors in Finnish children and adolescents. VII. Serum immunoreactive insulin. Acta Paediatr Scand [Suppl] 318: 127–133
Rönnemaa T, Knip M, Lautala P et al. (1991) Serum insulin and other cardiovascular risk indicators in children, adolescents and young adults. Ann Med 23: 67–72
Donahue RP, Skyler JS, Schneiderman B, Prineas RJ (1990) Hyperinsulinemia and elevated blood pressure: cause, confounder or coincidence? Am J Epidemiol 132: 827–836
KarhapÄÄ P, Uusitupa M, Voutilainen E, Laakso M (1992) Effects of bezafibrate on insulin sensitivity and glucose tolerance in subjects with combined hyperlipidemia. Clin Pharmacol Ther 52: 620–626
Riccardi G, Genovese S, Saldalamacchia G et al. (1989) Effects of bezafibrate on insulin secretion and insulin sensitivity in hyperlipidemic patients with and without diabetes. Atherosclerosis 75: 175–181
DeFronzo RA, Ferrannini E (1991) Insulin resistance a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 173–194
Lewis GF, Uffelman KD, Szeto LW, Steiner G (1993) Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. Diabetes 42: 833–842
Golay A, Zech L, Shi M-Z et al. (1987) Role of insulin in regulation of high density lipoprotein metabolism. J Lipid Res 28: 10–18
Applebaum-Bowden D, Haffner SM, Wahl PW et al. (1985) Postheparin plasma triglyceride lipases: relationships with very low density lipoprotein triglyceride and high density lipoprotein 2 cholesterol. Arteriosclerosis 5: 273–282
Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L (1981) Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 30: 219–225
DeFronzo RA, Cooke C, Andres R, Faloona GR, Davis PJ (1975) The effect of insulin in renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 55: 845–855
Standley PR, Bakir MH, Sowers JR (1993) Vascular insulin abnormalities, hypertension, and accelerated atherosclerosis. Am J Kidney Dis 21: 39–46
Thiebaud D, DeFronzo RA, Jacot E et al. (1982) Effect of long chain triglyceride infusion on glucose metabolism in man. Metabolism 31: 1128–1136
Julius S, Gudbrandsson T, Jamerson K, Tariq Shahab S, Andersson O (1991) The hemodynamic link between insulin resistance and hypertension. J Hypertens 9: 983–986
Smoak CG, Burke GL, Webber LS, Harsha DW, Srinivasan SR, Berenson GS (1987) Relation of obesity to clustering of cardiovascular disease risk factors in children and young adults. The Bogalusa Heart Study. Am J Epidemiol 125: 364–372
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Raitakari, O.T., Porkka, K.V.K., Rönnemaa, T. et al. The role of insulin in clustering of serum lipids and blood pressure in children and adolescents. Diabetologia 38, 1042–1050 (1995). https://doi.org/10.1007/BF00402173
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DOI: https://doi.org/10.1007/BF00402173