Hypertension in Diabetic Patients and Differences Between Insulin-Dependent Diabetes Mellitus and Non-Insulin-Dependent Diabetes Mellitus

Hypertension in Diabetic Patients and Differences Between Insulin-Dependent Diabetes Mellitus and Non-Insulin-Dependent Diabetes Mellitus

Hypertension in Diabetic Patients and Differences Between Insulin-Dependent Diabetes Mellitus and Non-Insulin-Dependent Diabetes Mellitus R.J. Jarrett...

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Hypertension in Diabetic Patients and Differences Between Insulin-Dependent Diabetes Mellitus and Non-Insulin-Dependent Diabetes Mellitus R.J. Jarrett, MD, FFCM • In insulin-dependent diabetes mellitus (100M), BP levels in subjects with normal or only mildly increased levels of albumin excretion do not differ systematically from those in non-diabetic reference populations. However, it is not known whether increased albuminuria and raised blood pressure are causally related. Several studies have observed higher average BP levels in glucose-intolerant subjects, even allowing for effects of age and adiposity. This applies to subjects with glucose intolerance below and above the World Health Organization criteria for diagnosing non-insulin-dependent diabetes mellitus (NIOOM). However, there are very few satisfactory studies comparing established patients with NIOOM with appropriate reference populations, and although it is widely believed that high BP (or hypertension) is a feature of NIOOM, the evidence for this belief is scant. © 1989 by the National Kidney Foundation, Inc. INDEX WORDS: Hypertension; diabetes; 100M; NIOOM.


HE LITERATURE on the topic of BP/ hypertension in diabetics compared with nondiabetics is extensive. Fortunately for the modern reviewer, much of this is redundant for several reasons: (1) failure to distinguish between insulindependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM); (2) lack of accompanying data on renal disease, particularly albumin excretion; (3) failure to take obesity into account in NIDDM; and (4) inappropriate selection of cases and/or controls. INSULIN-DEPENDENT DIABETES MELLITUS

Moss compared systolic BPs in 123 patients, aged 8 to 18 years, with IDDM and 889 controls, all attending neighboring summer camps. Average levels, apparently age-adjusted, were 3 to 4 mm Hg higher in diabetics, but there was no adjustment for duration and no measurement of urinary protein. Kaas Ibsen et al compared BP levels in 151 diabetic children aged 2 to 19 years with those in a Danish reference population. 2 Shortly after diagnosis systolic BP levels were similar but diastolic (phase 4) levels were significantly lower in From the Division of Community Medicine, United Medical and Dental Schools of Guy's and St Thomas' Hospitals (Guy's Campus), London. Address reprint requests to R.J. Jarrett, MD, FFCM, Division of Community Medicine, United Medical and Dental Schools of Guy's and St Thomas' Hospitals (Guy's Campus), London SE1 9RT, England. © 1989 by the National Kidney Foundation, Inc. 0272-6386/89/1301-0005$3.00/0


the diabetic children. After 5 years of diabetes, systolic levels remained similar in the two groups, and significantly lower diastolic levels were confined to female diabetics. Unfortunately, the BPs were measured in different positions-supine in the diabetics and sitting in the reference population. Cruickshanks et al measured blood pressure levels in 145 diabetics aged 9 to 16 years and compared them with 45 siblings of diabetics, not necessarily of the same diabetic probands. 3 Systolic BP on average was slightly and significantly higher in the diabetics of both sexes after age adjustment, but there was no significant difference in phase 4 diastolic levels. In girls phase 5 diastolic levels were higher in the diabetics. No adjustments were made for diabetes duration or for proteinuria. Tarn and Drury measured BP levels in the families participating in the Barts-Windsor study. 4 Measurements were made in 163 diabetics aged 4 to 32 years, 232 nondiabetic siblings, and 292 parents. Systolic pressures were not different overall nor in any 4-year age band, but phase 4 diastolic pressure was significantly higher (2.8 mm Hg) in diabetic males compared with their sibling group. There were no significant differences in diastolic pressure in the females in phase 4 or 5, nor in phase 5 in males. When mean BP above the 90th percentile for age and sex was considered, 17 % of the diabetics and 11 % of the siblings exceeded this value. It may be relevant that eight of 27 diabetics (29 %) in this category had increased albumin excretion, defined as a 24-hour urinary albumin excretion > 12 p,g/min or a random albumin concentration >30 mg/dL. Furthermore,

American Journal of Kidney Diseases, Vol XIII, No 1 (January), 1989: pp 14-16



in both diabetics and siblings with mean BP levels above the 90th percentile, the respective parent groups had significantly more cases of borderline (BP > 140/90) or treated hypertension than the parents of normotensive children. The importance of albuminuria is illustrated by the case-control study of Wiseman et al. 5 Subjects were taken from a screening program in the diabetic clinic in which overnight collections of urine were made for calculation of the albumin excretion rate (AER). All subjects were within 10% of ideal body weight with negative Albustix (Ames, Stoke Poges, England) tests for urinary protein, serum creatinine within the normal range, and no history of renal or urinary tract disease. Twenty-eight patients with AER above the normal range were identified and subdivided into two groups, 16 with AER < 30 {tg/min and 12 with AER > 30 {tg/min. These two groups, termed "low" and "high" microalbuminuria, respectively, were individually matched for age, duration, and gender with patients having AERs within the normal range. Four separate BP readings were taken in each subject by a single observer across the course of a day spent in a metabolic ward. Systolic and diastolic (phase 4) BP levels were not different between the low microalbuminuria group and its control. However, both diastolic and systolic levels were significantly higher in the high microalbuminuria group than in the controls and the low microalbuminuria group. An association between degree of albuminuria and level of BP in IDDM has been confirmed by other investigators. 6.7 NON-INSULIN-DEPENDENT DIABETES MELLITUS

Many studies of BP in NIDDM and reference populations do not control for degree of obesity, which is related to BP and tends to be greater in diabetics. Indeed, for this and other reasons, there are few studies worth quoting. In a population study of subjects aged 50 to 79 years in California,8 mean BP levels adjusted for age and body mass index (BMI) were lowest for nondiabetics, intermediate for newly detected disease, and highest for established diabetics, but the differences were small and were statistically significant only for women. In the Bedford survey, BP levels were compared between newly detected diabetics, borderline

diabetics (roughly equivalent to "impaired glucose tolerance"), and a normoglycemic reference population. 9 In men, age- and BMI-adjusted mean systolic values were significantly higher in both hyperglycemia groups, but diastolic values were higher only in the borderline diabetics. In women only the adjusted systolic values were significantly higher in the hyperglycemic groups. The Whitehall study was confined to men working in the civil service. 9 Each subject who was not a known diabetic had a blood glucose measurement two hours after a 50-g oral glucose load. Again, mean BP levels were higher in borderline and newly detected diabetics and, in multiple regression analysis, both systolic and diastolic BP levels were significantly and independently related to blood glucose levels. In the diabetics participating in the study, average BP levels were similar to those of the normoglycemic controls, but the representativity of the sample was not ascertained and they might in any case have been more accustomed to BP measurement. In the Framingham study,IO at examination 12, the prevalence of hypertension (systolic BP > 160 mm Hg; diastolic BP >90 mm Hg) in diabetics aged 50 to 79 years (presumably NIDDM) was higher than in nondiabetics. The difference was significant after adjustment for age and BMI; however, the dimensions of the difference after adjustment were not stated. Associations between blood glucose (and plasma insulin)-both fasting and postload-with BP, apparently independent of obesity, have been reported from several popUlation surveys.ll-14 Elevated BP may also be a weak predictor of subsequent diabetes, although this is confounded by obesity. 10.15 Thus, while glucose/insulin/BP are demonstrably associated variables, and average BP levels are higher in persons with glucose intolerance, both above and below the cut-off point for applying the label "diabetic," we know virtually nothing about any subsequent effect of diabetes on BP. Proteinuria and BP Whereas the association of raised BP and even modest degrees of proteinuria in IDDM is well.established, the situation in NIDDM is confused. In the study of Fabre et al 16 diastolic hypertension was positively associated with 24-hour protein ex-



cretion, but BP values were not adjusted for age or obesity. In the Bedford study, significant positive correlations were obtained between systolic BP and log AER in patients with newly detected diabetes. I? A positive correlation of low degree was also noted in subjects with fasting hyperglycemia, subjects with known diabetes, and control subjects in a population aged 60 to 74 years in Denmark. ls However, in another Danish study of patients stratified by duration and urinary albumin concen-

tration, there was no apparent association of urinary albumin concentration and Bp'19 In our comparison of Europid and Asian Indian NIDDM, we found a significant association of BP/hypertension and albumin/creatinine ratio in early morning urine samples in the Indians but not the Europids. 20 The lack of consistency may be in part due to methodological differences, but the association of BP and proteinuria appears to be less impressive in NIDDM than in IDDM.

REFERENCES I. Moss AJ: Blood pressure in children with diabetes mellitus. Pediatrics 30:932-936, 1962 2. Kaas Ibsen K, Rotne H, Hougaard P: Blood pressure in children with diabetes mellitus. Acta Paediatr Scand 72: 191196, 1983 3. Cruickshanks KJ, Orchard TJ, Becker DJ: The cardiovascular risk profile of adolescents with insulin dependent diabetes mellitus. Diabetes Care 8:118-124, 1985 4. Tarn AC, Drury PL: Blood pressure in children, adolescents and young adults, with Type 1 (insulin-dependent) diabetes. Diabetologia 29:275-281, 1986 5. Wiseman M, Viberti G, Mackintosh D, et al: Glycaemia, arterial pressure and micro-albuminuria in 'I)'pe 1 (insulindependent) diabetes mellitus. Diabetologia 26:401-405, 1984 6. Mathiesen ER, Oxenboll B, Johansen K, et al: Incipient nephropathy in 'I)'pe 1 (insulin-dependent) diabetes. Diabetologia 26:406-410, 1984 7. Mogensen CE, Christensen CK: Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311: 8993, 1984 8. Barrett-Connor E, Criqui MH, Klauber MR, et al: Diabetes and hypertension in a community of older adults. Am J Epidemiol 113:276-284, 1981 9. Jarrett RJ, Keen H, McCartney M, et al: Glucose tolerance and blood pressure in two population samples: Their relation to diabetes mellitus and hypertension. Int J Epidemiol 7:15-24,1978 10. Wilson PWF, Anderson KM, Kannel WB: Epidemiology of diabetes mellitus in the elderly: The Framingham study. Am J Med 80:3-9, 1986 (suppl 5A) II. Florey C du V, Uppal S, Lowy C: Relation between

blood pressure, weight, and plasma sugar and serum insulin levels in school children aged 9-12 years in Westland, Holland. Br Med J 1: 1368-1371, 1976 12. Burke GL, Webber LS, Srinavasan SR, et al: Fasting plasma glucose and insulin levels and their relationship to cardiovascular risk factors in children: Bogalusa Heart Study. Metabolism 35:441-446, 1986 13. Persky V, Dyer A, Stamler J, et al: The relationship between post-load plasma glucose and blood pressure at different resting heart rates. J Chron Dis 32:263-268, 1979 14. Cederholm J, Wibell L: Glucose intolerance in middleaged subjects-A cause of hypertension? Acta Med Scand 217:363-371, 1985 15. Medalie JH, Papier CM, Goldbourt U, et al: Major factors in the development of diabetes mellitus in 10,000 men. Arch Intern Med 135:811-817, 1975 16. Fabre J, Balant LP, Dayer PG, et al: The kidney in maturity onset diabetes mellitus: A clinical study of 510 patients. Kidney Int 21:730-738, 1982 17. Keen H, Chlouverakis C, Fuller JH, et al: The concomitants of raised blood sugar: Studies in newly-detected hyperglycaemics. Guy's Hosp Rep 118:247-254, 1969 18. Damsgaard EM, Mogensen CE: Microalbuminuria in elderly hyperglycaemic patients and controls. Diabetic Med 3:430-435, 1986 19. Mogensen CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356-360, 1984 20. Allawi J, Rao PY, Gilbert R, et al: Microalbuminuria in non-insulin-dependent diabetes: Higher frequency in Indian compared with Europid patients. Br J Med 296:462-464, 1988