intolerance, and others may delay the progression of diabetic complications. The Canadian Hypertension Society convened a consensus conference of national ...
I Consensus Conference Report
Recommendations from the Canadian Hypertension Society Consensus Conference on Hypertension and Diabetes* Pavel Hamet, MD, PhD Norman Kalant, MD, PhD Stuart A. Ross, MB, ChB Thomas W. Wilson, MD, MSc Frans H.H. Leenen, MD, PhD R. Brian Haynes, MD, PhD
A rterial hypertension and diabetes mellitus are common in adults and are associated with potentially serious consequences. Diabetes can cause hypertension through various mechanisms. If the two diseases occur together the occurrence and progression of complications are greatly accelerated. Some forms of therapy for hypertension may induce or aggravate glucose intolerance, and others may delay the progression of diabetic complications. The Canadian Hypertension Society convened a consensus conference of national and international experts to review the relation between hypertension and diabetes and to make recommendations for optimum management of hypertension in
*Conference chairman: Dr. Pavel Hamet, Montreal. Panel on Pathogenesis of Hypertension in Diabetes: Drs. Norman Kalant (chairman), Montreal; C. Erik Mogensen (invited guest), Aarhus, Denmark; John K McKenzie, Winnipeg; J. David Spence, London, Ont.; and George Steiner, Toronto. Panel on Prognosis of Diabetes with Hypertension: Drs. Stuart A. Ross (chairman), Calgary; A. Richard Christlieb (invited guest), Boston; Otto G. Kuchel, Montreal; and Alexander G. Logan, Toronto. Panel on Specificities of Antihypertensive Therapy: Drs. Thomas W. Wilson (chairman), Saskatoon; Hans-Henrik Parving (invited guest), Copenhagen; Keith G. Dawson, Vancouver; Pierre Larochelle, Montreal; and Bernard Zinman, Toronto. Panel on Research Needs and Directions: Drs. Pavel Hamet (chairman); Serge Carriere, Montreal; and Jean L. Chiasson, Montreal. Panel on Monitoring: Drs. Frans H.H. Leenen (chairman), Toronto; Harold Colburn, Ottawa; Jacques de Champlain, Montreal; and Francis Rolleston, Ottawa.
diabetic patients. This article summarizes the highlights of the conference and the main recommendations. Copies of the detailed proceedings are available from Dr. Pavel Hamet, Clinical Research Institute of Montreal, 110 Pine Ave. W, Montreal, PQ H2W 1R7. Pathogenetic features of hypertension in patients with diabetes Hypertension is more common in patients with diabetes mellitus, whether or not they are insulin dependent,1-3 than in nondiabetic subjects, even if the increased rate of obesity among diabetic patients is considered.2 The pathogenetic features of hypertension in diabetic patients without overt nephropathy differ from those in nondiabetic subjects, because the salt retention associated with diabetes4 is possibly secondary to hyperinsulinemia5 and because the response to the pressor effects of norepinephrine and angiotensin II is
increased.4'6'7
Albuminuria, which signifies early diabetic nephropathy, is associated with increased blood pressure.8'9 As diabetic nephropathy develops, renal function decreases; this effect plays a major role in the progression of hypertension. There is insufficient information to determine whether the pathogenetic features of hypertension differ between insulin-dependent and non-insulin-dependent patients.
The conference was supported by grants from the Department of National Health and Welfare and the Medical Research Council of Canada, Ottawa, and Fonds de la recherche en sante du Quebec, Montreal.
Recommendation
Reprint requests to: Dr. Pavel Hamet, Clinical Research Institute of Montreal, 110 Pine Ave. W, Montreal, PQ H2W 1R7
at university centres to confirm whether the condi-
Screening for albuminuria should be instituted CMAJ, VOL. 139, DECEMBER 1, 1988
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tion is an early marker of hypertension in diabetic patients and an indicator for early intervention and to assess the nature of albuminuria's association with increased rates of death from macrovascular disease among non-insulin-dependent patients.
Prognosis of diabetes associated with hypertension Hypertension accelerates the rate of renal and vascular complications associated with diabetes. Aggressive antihypertensive therapy can decrease the accelerated rate.10-12 Recommendations
* Patients with diabetes mellitus should be seen at least twice yearly for assessment. * Special attention should be given to monitoring the blood pressure, peripheral arterial circulation and urinary albumin levels; funduscopy should be performed by an ophthalmologist at least annually. * If hypertension is detected, adequate treatment should be instituted and the patient followed up closely. * Because hypertension and diabetes commonly occur together and because some antihypertensive drugs can induce or aggravate glucose intolerance, the hypertensive patient should also be monitored for the onset of diabetes.
Antihypertensive therapy in diabetes A previous consensus conference of the Canadian Hypertension Society dealt with the measurement of blood pressure and the diagnosis of hypertension; the recommendations"3 were accepted as still being current. The criteria for the diagnosis of diabetes mellitus of the Canadian Diabetes Association14 were also accepted.
being modified. As for all hypertensive patients, treatment should be started if the diastolic blood pressure is 100 mm Hg or greater. Additional recommendations were made as follows. * If the diastolic blood pressure is 90 to 99 mm Hg patients with hypertensive target organ damage (as indicated by stroke or transient ischemic attacks, coronary artery disease, enlargement or failure of the heart, peripheral arterial disease or renal impairment) should receive theraPY. * Diabetic patients with persistent proteinuria (0.5 g or more daily) or proliferative retinopathy should be treated for hypertension. * For patients with a diastolic blood pressure of 90 to 99 mm Hg without any hypertensive or diabetic vascular complications, antihypertensive therapy should be determined on an individual basis; other cardiovascular risk factors, such as smoking and abnormal blood lipid levels, should be considered. * For patients with isolated or predominantly systolic hypertension (pulse pressure greater than 80 mm Hg) the guidelines of the Consensus Conference on Hypertension in the Elderly16 should be followed. * The goal for treatment is a diastolic blood pressure below 90 mm Hg and, in most cases, a systolic blood pressure below 160 mm Hg. Recommendations for nonpharmacologic therapy
* Weight loss in obese patients is beneficial in the treatment of hypertension17 and diabetes18 whether or not the diabetes is insulin dependent. * Moderate restriction of salt intake (to levels of less than 150 mmol/d) should be considered an adjunct to definitive therapy in the hypertensive diabetic patient.19 More stringent restriction should be reserved for cases of severe hypertension. * Patients should be counselled about the consumption of alcohol, which increases blood pressure and blood glucose levels. Recommendations for drug therapy
Recommendations for monitoring of blood pressure * The high prevalence of orthostatic hypotension in diabetic patients15 warrants the routine monitoring of blood pressure while the patient is standing as part of assessment and follow-up. * Blood pressure readings for the purpose of diagnosis should not be taken when the patient is
hypoglycemic. Recommendations for initiation of therapy The existing guidelines for the treatment of hypertension were accepted,13 the treatment for diabetic patients with retinopathy or nephropathy 1060
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There have been no long-term comparative clinical trials of antihypertensive agents in diabetic patients. Furthermore, diabetic patients are not a homogeneous group, and no single regimen can be recommended in all cases. The antihypertensive drugs thought at the conference to be most useful for three groups of diabetics appear in Table I. * Non-insulin-dependent diabetic patients: Most diabetic patients can adequately control their blood sugar level through diet alone or diet and oral hypoglycemic therapy; therefore, the highest priority for antihypertensive drug therapy should be to avoid interference with metabolic control. Because unawareness of hypoglycemia is not a major problem for these patients, ,3-adrenergic blockers are particularly useful. However, non-
selective (3-blockers can cause deterioration in glycemic control; therefore, cardioselective ones and those with intrinsic sympathomimetic activity are preferable.20'2' Calcium-channel blockers, angiotensin-converting-enzyme (ACE) inhibitors, aadrenergic blockers and centrally acting agents are other drugs that do not affect glucose metabolism and can be added to, or substituted for, (3-blockers. Hydralazine hydrochloride, an arterial vasodilator, also does not affect glucose metabolism but must be given in combination with a (3-blocker or a centrally acting drug because of its tachycardic effect. Thiazide diuretics should generally not be used alone, although with low doses and careful maintenance of the serum potassium level (e.g., through the addition of a potassium-sparing diuretic) they may be successful.22 * Insulin-dependent diabetic patients: The hyperglycemic effect of some antihypertensive drugs is not of clinical importance for these patients. However, (3-blockers do interfere with the patient's awareness of and response to hypoglycemia. Thus, the recommendations for therapy are the same as those for hypertensive patients without diabetes except that (-blockers should be avoided or prescribed with caution and blood glucose levels should be monitored carefully.2" * Diabetic patients with nephropathy: Effective antihypertensive therapy is particularly important in these patients, because good control of blood pressure can slow the progression of renal failure.'0"' Diuretics have the additional benefit of correcting the hypervolemia that is frequently associated with renal failure. It is particularly Table I - Recommended drug therapy for hypertension in patients with diabetes mellitus
Non-insulin-dependent patients Selective (3-adrenergic blockers or those with intrinsic sympathomimetic activity Calcium-channel blockers Angiotensin-converting enzyme (ACE) inhibitors a-adrenergic blockers Centrally acting agents Arterial vasodilators* Diuretics Insulin-dependent patients Thiazide diuretics ACE inhibitors Calcium-channel blockers Centrally acting agents
f-adrenergic blockers a-adrenergic blockers Arterial vasodilators* Diabetic patients with nephropathy Thiazide or loop diuretics Low-dose selective f3-adrenergic blockers Hydralazine hydrochloride* ACE inhibitors Calcium-channel blockers Centrally acting agents a-adrenergic agents *In combination with 3-adrenergic blockers or centrally acting agents.
important to select agents that not only decrease the severity of systemic hypertension but also improve the glomerular pressure. ACE inhibitors appear to have these properties and may ultimately be the preferred drugs;23'24 however, they can also lead to life-threatening hyperkalemia and therefore necessitate close monitoring. Research needs and directions Many aspects of the nature and management of hypertension among diabetic patients in Canada have yet to be studied. A substantial number of research initiatives are required in the areas of epidemiology, treatment and basic research; these recommendations are outlined in the proceedings of the conference. A new guide to the practical management of hypertension in patients with diabetes in primary care settings is available, with a companion pamphlet for patients, at no cost from the Canadian Hypertension Society. Contact Dr. R. Brian Haynes, Rm. 3H8, McMaster University Medical Centre, 1200 Main St. W, Hamilton, Ont. L8N 3Z5.
References 1. Pell S, D'Alonzo CA: Some aspects of hypertension in diabetes mellitus. JAMA 1967; 202: 104-110 2. Barrett-Connor E, Criqui MH, Klauber MR et al: Diabetes and hypertension in a community of older adults. Am J Epidemiol 1981; 113: 276-284 3. Christlieb AR, Warram JH, Krolewski AS et al: Hypertension: the major risk factor in juvenile-onset insulin-dependent diabetics. Diabetes 1981; 30 (suppl 2): 90-96 4. Weidmann P, Trost BN: Pathogenesis and treatment of hypertension associated with diabetes. Horm Metab Res [Suppl] 1985; 15: 51-58 5. DeFronzo RA: The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 1981; 21: 165-171 6. Drury PL, Smith GM, Ferriss JB: Increased vasopressor responsiveness to angiotensin II in uncomplicated type I (insulin-dependent) diabetic patients without complications. Diabetologia 1984; 27: 174-179 7. Christlieb AR, Janla HU, Kraus B et al: Vascular reactivity to angiotensin II and norepinephrine in diabetic subjects. Diabetes 1976; 25: 268-274 8. Mogensen CE, Christensen CK, Vittinghus E: The stages in diabetic renal disease with emphasis on the stage of incipient nephropathy. Diabetes 1983; 32 (suppl 2): 64-68 9. Viverti GC, Jarrett RJ, Mahmud U et al: Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982; 1: 1430-1432 10. Mogensen CE: Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment. Scand J Clin Lab Invest 1976; 36: 383388 11. Parving HH, Andersen AR, Smidt UM et al: Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983; 1: 1175-1179 12. Chahal P, Inglesby DV, Sleightholm M et al: Blood pressure and the progression of mild background diabetic retinopathy. Hypertension 1985; 7 (suppl 2): 79-83 13. Logan AG: Report of the Canadian Hypertension Society's CMAJ, VOL. 139, DECEMBER 1, 1988
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14.
15. 16. 17. 18. 19.
consensus conference on the management of mild hypertension. Can Med AssocJ 1984; 131: 1053-1057 Ad Hoc Committee on Diagnostic Criteria for Diabetes Mellitus, Clinical and Scientific Section, Canadian Diabetes Association: Acceptance of new criteria for diagnosis of diabetes mellitus and related conditions by the Canadian Diabetes Association. Can Med AssocJ 1982; 126: 473-476 Clarke BF, Ewing DJ, Campbell IW: Diabetic autonomic neuropathy. Diabetologia 1979; 17:195-212 Larochelle P, Bass MJ, Birkett NJ et al: Recommendations from the Consensus Conference on Hypertension in the Elderly. Can Med AssocJ 1986; 135: 741-745 Reisin E, Frohlich ED: Effects of weight reduction on arterial pressure. J Chronic Dis 1982; 35: 887-891 Lipson LG, Lipson M: The therapeutic approach to the obese maturity-onset diabetic patient. Arch Intern Med 1984; 144: 135-138 Ram CVS, Garrett BN, Kaplan NM: Moderate sodium
Meetings
con tin ued from page 1043 Apr. 2-5, 1989: COACH Conference XIV: Putting Technology into Care Sheraton Centre, Toronto Steven A. Huesing, executive director, Canadian Organization for Advancement of Computers in Health, 1200-10460 Mayfield Rd., Edmonton, Alta. T5P 4P4; (403) 489-4553 Apr. 7, 1989: Anesthesia for Non-Specialists Royal Victoria Hospital, Montreal Postgraduate Board, Royal Victoria Hospital, 687 Pine Ave. W, Montreal, PQ H3A lA1; (514) 842-1231, ext. 5300 Apr. 7, 1989: Update: Hematology Hotel Nova Scotian, Halifax Christine Smith, director, Continuing Medical Education, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, NS B3H 4H7; (902) 424-2061 Apr. 12-15, 1989: North American Primary Care Research Group Conference Hilton Palacio del Rio Hotel, San Antonio, Texas Continuing Medical Education Office, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78284-7980, USA; (512) 567-4444 Apr. 13-14, 1989: Obstetrics and Gynecology World Trade and Convention Centre, Halifax Liz Poulsen, program coordinator, Continuing Medical Education, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, NS B3H 4H7; (902) 424-2062 Apr. 14, 1989: Urinary Tract Problems in Family Practice Sir Mortimer B. Davis Jewish General Hospital, Montreal Dr. M. Malus, Herzl Family Practice Unit, Sir Mortimer B. Davis Jewish General Hospital, 3755 C6te Ste-Catherine Rd., Montreal, PQ H3T 1E2; (514) 340-8253, ext. 4728
Apr. 17-22, 1989: 3rd Cuban and International Seminar on Interferon, 2nd Cuban and International Seminar 1062
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20. 21.
22.
23. 24.
restriction and various diuretics in the treatment of hypertension. Arch Intem Med 1981; 141: 1015-1019 Groop L, Totterman KJ, Harno K et al: Influence of beta-blocking drugs on glucose metabolism in patients with diabetes mellitus. Acta Med Scand 1982; 211: 7-12 Schluter KJ, Aellig WH, Petersen KG et al: The influence of ,B-adrenoceptor blocking drugs with and without intrinsic sympathomimetic activity on the hormonal responses to hypo- and hyperglycaemia. Br J Clin Pharmacol 1982; 13: 407s-417s Struthers AD: The choice of antihypertensive therapy in the diabetic patient. Postgrad MedJ 1985; 61: 563-569 Hommel E, Parving HH, Mathiesen E et al: Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. Br MedJ 1986; 293: 467-470 Bjorck S; Nyperg G, Mulec H et al: Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. Ibid: 471-474
on Biotechnology and 1st Iberoamerican Congress on Biotechnology International Conference Center, Havana Abstract deadline is Jan. 20, 1989. Interferon and Biotechnology '89, Apartado 6162 Cubanacan, La Habana, Cuba; tel. 20-1402, FAX 21-8070
Apr. 23-27,1989: National Conference of the Canadian Association of Emergency Physicians and INTERPHASE (Prehospital Personnel of Canada) Banff Springs Hotel, Banff, Alta. Brian Winter, PO Box 10, Cochrane, Alta. TOL OWO
May 2-6, 1989: Obstetrics and Gynecology Refresher Course King Edward Hotel, Toronto Continuing Medical Education, Faculty of Medicine, Medical Sciences Building, University of Toronto, Toronto, Ont. M5S 1A8; (416) 978-2718 May 4-5, 1989: 21st Annual Course in Drug Therapy Hotel Ritz Carleton, Montreal Postgraduate Board, Montreal General Hospital, 7111-1650 Cedar Ave., Montreal, PQ H3G 1A4; (514) 934-1779
May 5, 1989: Update: Respirology Holiday Inn, Halifax Christine Smith, director, Continuing Medical Education, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, NS B3H 4H7; (902) 424-2061 May 12,1989: Update: Otolaryngology Hotel Nova Scotian, Halifax Christine Smith, director, Continuing Medical Education, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, NS B3H 4H7; (902) 424-2061 May 12-13, 1989: 2nd Annual Conference: Update in Emergency Medicine Harbour Castle Westin Hotel, Toronto Gayle Willoughby, Department of Emergency Medicine, North York General Hospital, 4001 Leslie St., Willowdale, Ont. M2K lE1; (416) 756-6165
continued on page 1074
