© 1999 American Heart Association, Inc.
Original Contributions |
Poor Glycemic Control Predicts Coronary Heart Disease Events in Patients With Type 1 Diabetes Without Nephropathy
From the Department of Medicine (S.L., K.P., M.L.), Kuopio University Hospital, Kuopio; and the Department of Medicine (T.R.), Turku University Central Hospital, and the Social Insurance Institution (T.R.), Turku, Finland.
Correspondence to M. Laakso, Department of Medicine, Kuopio University Hospital, SF-70210 Kuopio, Finland. E-mail markku.laakso{at}uku.fi
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Abstract |
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Abstract—Patients with type 1 diabetes mellitus, especially those with nephropathy, are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to CHD events in patients with type 1 diabetes without nephropathy is still incomplete. Therefore, we performed a prospective study on risk factors for CHD in patients with type 1 diabetes free of clinical nephropathy. At baseline examination, cardiovascular risk factor levels of CHD were determined in 177 patients with type 1 diabetes (87 men and 90 women), age 45 to 64 years at baseline and
30 years at the time of diagnosis
of diabetes. These patients were followed up to 7 years with respect to
CHD events. Altogether, 20 patients with type 1 diabetes (13 men
[7.3%] and 7 women [3.9%]) died of CHD and 28 patients with type
1 diabetes (17 men [9.6%] and 11 women [6.2%]) had a serious CHD
event (death from CHD or nonfatal myocardial infarction). In
multivariate Cox regression analysis, a
previous history of myocardial infarction (hazard ratio [HR]
and its 95% confidence interval, 8.0 [3.1 to 21.0],
P<0.001), high glycohemoglobin A1
(>10.4%, the highest tertile, HR 5.4 [1.4 to 20.4],
P=0.013), and the duration of diabetes (>16
years, the highest tertile, HR 4.2 [1.3 to 12.9],
P=0.013) were the only variables associated with CHD
death even after adjustment for other cardiovascular
risk factors. These variables also predicted the incidence of all
CHD events. Our results indicate that poor metabolic
control is a strong predictor of CHD events in patients with late-onset
type 1 diabetes without nephropathy, independently of other
cardiovascular risk factors.
Key Words: type 1 diabetes • glucose • glycohemoglobin A1 • coronary heart disease
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Introduction |
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Several studies have indicated that mortality and morbidity rates of coronary heart disease (CHD) are 2 to 4 times higher among patients with type 1 diabetes than in age-matched nondiabetic subjects.1 2 In particular, patients with clinical diabetic nephropathy and a long duration of diabetes have an extremely high morbidity from macrovascular disease.2 3 4 5 Proteinuria and microalbuminuria in patients with type 1 diabetes are known to be associated with several adverse cardiovascular risk factors, including hypertension and lipoprotein abnormalities, characterized mainly by elevated serum total and LDL cholesterol and high total and VLDL triglyceride levels, low HDL cholesterol, and low ApoA1 levels.6 7 8 Chronic hyperglycemia9 10 11 12 and poor glycemic control13 14 15 16 have been implicated in the pathogenesis of microvascular complications in patients with type 1 diabetes, but little data are available on the role of these factors for the development of macrovascular complications.
Prospective studies based on representative cohorts of patients with late-onset type 1 diabetes and without clinical diabetic nephropathy, in whom cardiovascular risk factors including serum lipids, lipoproteins, and indicators of glycemic control had been measured at baseline, were not available. This information is, however, particularly relevant because a high occurrence of CHD in patients with type 1 diabetes with nephropathy could be caused mainly by adverse effects of renal disease on cardiovascular risk factors and not by the diabetes state itself.17 Therefore, we performed a prospective study on risk factors for CHD in representative cohorts of Finnish patients with late-onset type 1 diabetes and without nephropathy.
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Methods |
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Subjects
Baseline Study
A cross-sectional study aiming to compare the prevalence of atherosclerotic vascular disease and its risk factors in middle-aged diabetic patients and in nondiabetic subjects was performed from 1982 to 1984 in eastern and western Finland. A detailed description of the procedure of obtaining representative study populations has been reported elsewhere.18 The study population was chosen from the national register of the Social Insurance Institution, which includes all Finnish citizens who receive antidiabetic medication. In brief, the inclusion criteria were the following: (1) age from 45 to 64 years, (2) diabetes diagnosed at the age of 30 years or later, and (3) area of residence and place of birth in the Kuopio University Hospital district (eastern Finland) or in the Turku University Hospital district (western Finland). Altogether, 567 diabetic patients from eastern Finland and 639 diabetic patients from western Finland participated (participation rates were 83% and 73%, respectively). Of these diabetic patients, 120 from eastern Finland and 158 patients from western Finland had insulin treatment at the time of examination. C-peptide measurements after intravenous glucagon were performed in 112 of the insulin-treated patients from eastern Finland and in 151 patients from western Finland (93% and 96%, respectively). In 228 patients, type 1 diabetes was diagnosed by postglucagon C-peptide measurement (<0.20 nmol/L) and a history of ketoacidosis. In all of these patients insulin treatment had been initiated within the first year after diagnosis. The cutoff point of 0.20 nmol/L was chosen because postglucagon C-peptide values below this limit have been shown to be associated with the occurrence of ketoacidosis in insulin-treated diabetic subjects.19 These 228 patients (113 men and 115 women) formed the study population. Fifty-one patients (26 men and 25 women) with urinary protein excretion >300 mg/L and/or serum creatinine >110 µmol/L in women and 120 µmol/L in men were excluded. Thus, the final study population comprised 177 patients (87 men and 90 women).
The study program previously described in detail18 was performed during 1 outpatient visit at the Clinical Research Unit of the University of Kuopio or the Rehabilitation Research Center of the Social Insurance Institution in Turku. The visit included an interview regarding the history of chest pain symptoms suggestive of CHD, smoking, alcohol intake, physical activity, and the use of drugs. All medical records of those subjects who reported during the interview that they had been admitted to the hospital because of chest pain symptoms were reviewed. Review of the medical records was performed by 2 of us (M.L. in Kuopio and T.R. in Turku) after a careful standardization of the methods between the reviewers. The World Health Organization criteria for verified definite or possible myocardial infarction (MI) based on chest pain symptoms, ECG changes, and enzyme determinations were used in the ascertainment of the diagnosis of previous MI.20
Smoking status was based on an interview. In all statistical analyses, subjects were classified as nonsmokers or current smokers.
With the subject in a sitting position after a 5-minute rest, blood pressure was measured with a mercury sphygmomanometer and read to the nearest 2 mm Hg. A subject was classified as having hypertension if he or she was receiving drug treatment for hypertension or if his or her systolic blood pressure was at least 160 mm Hg or diastolic blood pressure at least 95 mm Hg.
Biochemical Methods
All laboratory specimens were drawn after a 12-hour fast at 8
AM. Fasting plasma glucose was determined by the glucose
oxidase method (Boehringer). Glycohemoglobin
A1 (GHbA1) was determined
by affinity chromatography (Isolab) (reference range,
5.5% to 8.5%). The plasma C-peptide response to glucagon was
determined according to the method of Faber and Binder.21
Serum lipids and lipoproteins were determined from fresh serum samples
drawn after a 12-hour overnight fast. Serum total
cholesterol and triglycerides were assayed by
automated enzymatic methods (Boehringer). Serum HDL
cholesterol was determined enzymatically after
precipitation of LDL and VLDL lipoproteins with dextran
sulfate/MgCl2.22 LDL
cholesterol was calculated by using the Friedewald formula
as follows: LDL cholesterol=total
cholesterol-HDL cholesterol-0.45xtotal
triglycerides.
Follow-Up Study
In 1990, a postal questionnaire containing questions about
hospitalization because of acute chest pain was sent to every surviving
participant of the original study cohort. All medical records of
those subjects who died between the baseline examination and December
31, 1989, or who reported in the questionnaire that they had been
admitted to the hospital because of chest pain symptoms between the
baseline examination and December 31, 1989, were reviewed by 1 of us
(S.L.). To ensure that the data collection with regard to
hospital-treated MIs was complete, a computerized hospital discharge
register was used to check hospital admissions of all participants of
the baseline study, and in case of hospitalization for an acute CHD
event, medical records were checked. The modified World Health
Organization criteria for definite or possible MI based on chest pain
symptoms, ECG changes, and enzyme determinations were used in the
ascertainment of the diagnosis of MI similarly as in the baseline
study.20 Copies of death certificates of those patients
who had died were obtained from the files of the Central Statistical
Office of Finland. In the final classification of the causes of death,
hospital records and autopsy records were used, if available.
The mortality data included in the present article are mortality
from CHD (International Classification of Diseases 9, Codes 410 to
414).
Statistical Methods
Data analyses were conducted with the SPSSX and
SPSS/PC+ programs (SPSS Inc). The results for continuous variables
are given as mean±SEM values or percentages. The differences between
the groups were assessed by the 
2 test, or
Student's 2-tailed t test for independent samples when
appropriate. The univariate and
multivariate Cox regression model23
was used to investigate the association of
cardiovascular risk factors with the incidence of CHD
events.
Approval of Ethics Committee
This study was approved by the Ethics Committee of Kuopio
University Central Hospital and the Turku University Central Hospital.
All study subjects gave informed consent.
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Results |
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During 7-year follow-up (mean follow-up was 7.2 years in men and women), 20 patients (13 men [7.3%] and 7 women [3.9%] women) with type 1 diabetes died of CHD. Altogether, 28 patients with type 1 diabetes (17 men [9.6%] and 11 women [6.2%]) had a serious CHD event (death from CHD or nonfatal MI).
Table 1
summarizes baseline
characteristics of patients with type 1 diabetes, in relation to
cardiovascular mortality and morbidity during the
7-year follow-up, by sex. Data from eastern and western Finland were
combined, because no significant differences existed between these
areas in the levels of cardiovascular risk factors with
respect to CHD events. Men with CHD were significantly older and had
more often a history of previous MI and had higher
GHbA1 than men without CHD. Women with CHD had
more often a history of previous MI and higher levels of
GHbA1 and a longer duration of diabetes than
women without CHD.
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Table 2 reports unadjusted and adjusted
hazard ratios (HRs) for cardiovascular risk factors.
The highest or lowest (for HDL cholesterol) tertile limit
was used as a cutoff point for continuous variables. In
univariate analysis, a previous history of MI and
GHbA1 and the duration of diabetes were the only
variables associated with the risk of CHD death
(P<0.001) and all CHD events (P<0.01). Figure 1 demonstrates that poor glycemic control
was associated with the incidence of CHD death similarly throughout the
follow-up period. In multivariate analysis, a
previous history of MI (HR 8.0 [3.1 to 21.0], P<0.001),
high GHbA1 (>10.4%, HR 5.4 [1.4 to 20.4],
P=0.013), and the duration of diabetes (>16 years, HR 4.2
[1.3 to 12.9], P=0.013) were associated with CHD death
even after adjustment for other cardiovascular risk
factors (age, sex, area of residence, previous MI, smoking, body mass
index, hypertension, total cholesterol, total
triglycerides, and HDL cholesterol). In a
similar manner, previous MI, high GHbA1, and a
long duration of diabetes were associated significantly with all CHD
events in univariate analyses.
Multivariate Cox analyses demonstrated that HRs
for previous MI (3.4 [1.5 to 7.9], P=0.004), high
GHbA1 (2.8 [1.2 to 6.9], P=0.021),
and long duration of diabetes (HR 3.9 [1.6 to 9.3],
P=0.002) remained almost unchanged when adjusted for other
cardiovascular risk factors. Because lipids and
lipoproteins were not associated with the risk for CHD, we included
these variables into the Cox regression models also as continuous
variables. In addition, we used different cutoff points to confirm
that the use of the highest tertile limit does not underestimate the
significance of these variables. Dyslipidemia was not a
significant risk factor in any of these analyses.
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10.4%) during the 7-year follow-up
(univariate Cox regression model).We did all statistical analyses also by including patients with nephropathy in our analyses (data not shown). These analyses also demonstrated that poor glycemic control (high GHbA1) was the strongest predictor for CHD death or for all CHD events. In a similar manner, the exclusion of patients with a history of MI before the baseline study (9 men and 7 women) did not change the results (data not shown).
We also analyzed whether the predictive value of poor
glycemic control with respect to CHD death was modified by the duration
of diabetes (Figure 1
). Median values of
GHbA1 (10.0%) and known duration of diabetes
(13.0 years) were used as cutoff points. The impact of poor glycemic
control on the risk for CHD death was seen independently of diabetes
duration. Although the long duration of diabetes increased the risk for
CHD death, this effect was much weaker than that exercised by
poor metabolic control (Figure 2).
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Discussion |
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Our 7-year follow-up study is the first population-based study demonstrating the important role of glycemic control as a predictor of CHD mortality and morbidity in patients with late-onset type 1 diabetes without nephropathy. In univariate analysis, the risk for CHD death was 7-fold and the risk for all CHD events (CHD death or nonfatal MI) 3-fold among patients with type 1 diabetes with high GHbA1 (>10.4%) compared with those with better glycemic control. The association remained statistically significant even after adjustment for other cardiovascular risk factors (Table 2
). Furthermore, the impact of poor glycemic
control was independent of diabetes duration. Because our study was
based on only 1 single measure of glycemic control at baseline, it is
likely that our results are even an underestimation of the deleterious
effects of hyperglycemia on the risk for CHD. Several previous studies have indicated that hyperglycemia predicts microvascular complications in patients with type 1 diabetes.10 11 12 Data on the risk for macrovascular complications have been much more limited. Deckert et al24 followed 259 patients with type 1 diabetes and with slightly elevated urinary albumin excretion (age range, 19 to 51 years at baseline) for 11 years. Elevated albumin excretion rate, but not GHbA1c, predicted the incidence of atherosclerotic vascular disease (CHD, stroke, and peripheral vascular disease). GHbA1 was also not a predictor for CHD in the Pittsburgh Epidemiology of Diabetes Complications Study.25 These 2 recent studies have significant differences compared with our study. Both included a much younger cohort of type 1 patients with early-onset diabetes. Furthermore, the study by Lloyd et al25 included patients with overt nephropathy, and the study by Deckert et al24 combined all manifestations of atherosclerotic vascular disease as their end point, which makes it impossible to clarify risk factors for CHD in their study. That poor metabolic control is causally associated with the risk for macrovascular complications in type 1 diabetes has recently gained substantial support by the Diabetes Control and Complications Trial.26 This trial demonstrated that not only microvascular complications, but also macrovascular complications, were reduced (by 41%) in patients with type 1 diabetes with good glycemic control compared with conventionally treated diabetic patients, although the reduction in macrovascular events was not statistically significant.
In patients with type 1 diabetes, total cholesterol,
HDL cholesterol, and total triglycerides are
usually within normal limits when blood glucose is
controlled.27 28 Good glycemic control in type 1 diabetes
usually reduces LDL and VLDL to normal levels29 and may
raise HDL even above the normal range.28 Abnormal
lipoprotein metabolism could theoretically contribute to
premature atherosclerosis in patients with type 1
diabetes. However, in our study, high levels of total and LDL
cholesterol and total triglycerides and low
levels of HDL cholesterol failed to predict CHD events in
patients with type 1 diabetes although our study population included a
substantial number of patients with poor metabolic control
(Table 2). This could be the result of a limited number of CHD
events in our study population, but it may also indicate that in
late-onset type 1 diabetes without nephropathy,
abnormalities in lipids and lipoproteins do not play such a crucial
role in the development of CHD compared with the effects of poor
glycemic control. Smoking, hypertension, and insulin dose were no
different among patients with type 1 diabetes with and without CHD
(Table 1).
Our study population including patients with type 1 diabetes
without nephropathy provided an excellent opportunity to
assess the relation between glycemic exposure and the risk for CHD in
type 1 diabetes. Based on our findings, it is suggested that the
crucial factor in the development of CHD in patients with late-onset
type 1 diabetes is hyperglycemia, because the only factors that
significantly predicted CHD events in our patients were high
GHbA1 and the long duration of diabetes (duration
of hyperglycemia). This implies that the risk for CHD in our study must
be explained by direct effects of hyperglycemia itself, because
clinical and biochemical characteristics were not otherwise different
between those who had a CHD event compared with those who did not
(Table 1). However, long-lasting hyperglycemia often leads to
diabetic kidney disease and cardiovascular risk factors
become abnormal when microalbuminuria, proteinuria, or
elevation of creatinine level are present. Therefore,
in addition to direct harmful effects of hyperglycemia, indirect
effects on cardiovascular risk factors also take place
that probably explain the massive increase in the risk for CHD in
patients with type 1 diabetes and overt nephropathy.
Many potential biochemical and clinical mechanisms may explain why hyperglycemia itself, independently of changes in cardiovascular risk factors, can increase the risk for CHD.30 Hyperglycemia is related to abnormalities in lipoprotein particle composition, which in turn are known to be atherogenic. Furthermore, hyperglycemia has been reported to accelerate oxidation of lipoproteins31 and to induce and worsen insulin resistance and hyperinsulinemia, both of these effects being linked with an increased risk for atherosclerotic vascular disease.32 33 34 35 Hyperglycemia can also accelerate thrombus formation among diabetic patients.36 37 Finally, long-lasting hyperglycemia can cause irreversible glycation of proteins in the arterial wall, which may also contribute to the development of vascular complications.37
Significant differences exist between type 1 diabetes and type 2 diabetes regarding cardiovascular risk factors predicting CHD. In type 2 diabetes, dyslipidemia (high LDL cholesterol, high total triglycerides, and low HDL cholesterol) is the most important determinant of CHD events.38 According to recent studies, hyperglycemia is also associated with the risk for CHD in type 2 diabetes but it is a weaker risk factor for CHD than is dyslipidemia.39 In contrast, according to the present study, poor metabolic control dominates other risk factors, including dyslipidemia, in patients with type 1 diabetes without diabetic kidney disease. Whether the relation between GHbA1 and the risk for CHD is linear or nonlinear cannot be solved by this study because of a limited number of CHD events.
Because poor glycemic control plays an important role in the development of macrovascular complications in type 1 diabetes, it is reasonable to assume that its treatment reduces the risk for CHD in patients with type 1 diabetes. The findings of the Diabetes Control and Complications trial are also in accordance with this view.26 Therefore, the correction of hyperglycemia seems to be rational, not only because of the prevention of microvascular complications, but also because it may decrease the risk for atherosclerotic vascular disease in patients with type 1 diabetes.
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Acknowledgments |
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This work was supported by grants from the Academy of Finland, the Finnish Heart Research Foundation, and the Aarne and Aili Turunen Foundation (to M.L. and S.L.).
Received August 5, 1998; accepted September 22, 1998.
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References |
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|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Pyörälä K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev. 1987;3:463–524.[Medline] [Order article via Infotrieve]
2. Krolewski AS, Kosinski EJ, Warram JH, Leland OS, Busick EJ, Asmal AC, Rand LI, Christlieb AR, Bradley RF, Kahn CR. Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus. Am J Cardiol. 1987;59:750–755.[Medline] [Order article via Infotrieve]
3. Koivisto VA, Stevens LK, Mattock M, Ebeling P, Muggeo M, Stephenson J, Idzior-Walus B. Cardiovascular disease and its risk factors in IDDM in Europe. Diabetes Care. 1996;19:689–697.[Abstract]
4. Jensen T, Borch-Johnsen K, Kofoed-Enevoldsen A, Deckert T. Coronary heart disease in young type 1 (insulin dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors. Diabetologia. 1987;30:144–148.[Medline] [Order article via Infotrieve]
5. Borch-Johnsen K, Kreiner S. Proteinuria-value as predictor of cardiovascular mortality in insulin-dependent diabetes mellitus. BMJ. 1987;294:1561–1564.
6. Howard BV, Savage BJ, Bennion LJ, Bennett PH. Lipoprotein composition in diabetes mellitus. Atherosclerosis. 1978;30:153–162.[Medline] [Order article via Infotrieve]
7. Goldberg RB. Lipid disorders in diabetes. Diabetes Care. 1981;4:561–572.[Abstract]
8. Briones ER, Mao SJT, Palumbo PJ, O'Fallon WM, Chenoweth W, Kottke BA. Analysis of plasma lipids and lipoproteins in insulin-dependent and non-insulin-dependent diabetics. Metabolism. 1984;33:42–49.[Medline] [Order article via Infotrieve]
9. Siperstein MD. Diabetic microangiopathy and the control of blood glucose. N Engl J Med. 1983;309:1577–1579.[Medline] [Order article via Infotrieve]
10. Teuscher A, Schnell H, Wilson PW. Incidence of diabetic retinopathy and relationship to baseline plasma glucose and blood pressure. Diabetes Care. 1988;11:246–251.[Abstract]
11.
Chase HP, Jackson WE, Hoops SL, Cockerham RS, Archer
PG, O'Brien D. Glucose control and the renal and retinal complications
of insulin-dependent diabetes. JAMA. 1989;261:1155–1160.
12.
Klein R, Klein BE, Moss SE, Cruickshanks KJ.
Relationship of hyperglycemia to the long-term incidence and
progression of diabetic retinopathy. Arch Intern
Med. 1994;154:2169–2178.
13. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4400 patients observed between 1947 and 1973. Diabetes Care. 1978;1:168–188.
14. Janka HU, Warram JH, Rand LI, Krolewski AS. Risk factors for progression of background retinopathy in long-standing IDDM. Diabetes. 1989;38:460–464.[Abstract]
15. D'Antonio JA, Ellis D, Doft BH, Becker DJ, Drash AL, Kuller LH, Orchard TJ. Diabetes complications and glycemic control: the Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report after 5 yr of IDDM. Diabetes Care. 1989;12:694–700.[Abstract]
16.
Klein R, Klein BE, Moss SE, Davis MD, De Mets DL.
Glycosylated hemoglobin predicts the incidence and progression of
diabetic retinopathy. JAMA. 1988;260:2864–2871.
17. Borch-Johnsen K, Kremer S. Proteinuria: value as predictor of cardiovascular mortality in insulin-dependent diabetes mellitus. BMJ. 1987;294:1651–1654.
18. Laakso M, Rönnemaa T, Pyörälä K, Kallio V, Puukka P, Penttilä I. Atherosclerotic vascular disease and its risk factors in non-insulin-dependent diabetic and nondiabetic subjects in Finland. Diabetes Care. 1988;11:449–463.[Abstract]
19. Madsbad S, Alberti KG, Binder C, Burrin JM, Faber OK, Krarup T, Regeur L. Role of residual insulin secretion in protecting against ketoacidosis in insulin-dependent diabetes. BMJ. 1979;2:1257–1259.
20. World Health Organization. Proposal for the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease and Protocol (MONICA Project). WHO/MNC/82.1 Rev. 1. Geneva, Switzerland: World Health Organization; 1983.
21. Faber OK, Binder C. C-peptide response to glucagon: a test for the residual B-cell function in diabetes mellitus. Diabetes. 1977;26:605–610.[Abstract]
22. Kostner G. Enzymatic determination of cholesterol in high density lipoprotein fractions prepared by polyanion precipitation. Clin Chem. 1976;22:695.
23. Cox DR. Regression models and life-tables. J R Stat Soc. 1972;34:187–201.
24.
Deckert T, Yokoyama H, Mathiesen E, Ronn B, Jensen T,
Feldt-Rasmussen B, Borch-Johnsen K, Jensen JS. Cohort study of
predictive value of urinary albumin excretion for
atherosclerotic vascular disease in patients with insulin dependent
diabetes. BMJ. 1996;312:871–874.
25.
Lloyd CE, Kuller LH, Ellis D, Becker DJ, Wing RR,
Orchard TJ. Coronary artery disease in IDDM: gender differences
in risk factors but not risk. Arterioscler Thromb Vasc Biol. 1996;16:720–726.
26.
The Diabetes Control and Complications Trial Research
Group. The effect of intensive treatment of diabetes on the development
and progression of long-term complications in insulin-dependent
diabetes mellitus. N Engl J Med. 1993;329:977–986.
27. Nikkilä EA. Plasma lipid and lipoprotein abnormalities in diabetes. In: Jarrett RJ, ed. Diabetes and Heart Disease. Amsterdam, The Netherlands: Elsevier Science Publishers, B.V.; 1984:134–167.
28. Nikkilä EA, Hormila P. Serum lipids and lipoproteins in insulin-treated diabetics. Demonstration of increased high density lipoprotein concentrations. Diabetes. 1978;27:1078–1085.[Medline] [Order article via Infotrieve]
29. Rosenstock JG, Vega GL, Raskin P. Improved diabetic control decreases LDL apoB synthesis in type I diabetes mellitus. Arteriosclerosis. 1985;5:513A.
30. Ruderman NB, Williamson JR, Brownlee M. Glucose and diabetic vascular disease. FASEB J. 1992;6:2905–2914.[Abstract]
31. Lyons TJ. Lipoprotein glycation and its metabolic consequences. Diabetes. 1992;41(suppl 2):67–73.
32. Pyörälä K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care. 1972;2:131–141.[Abstract]
33. Ducimetiere P, Eschwege E, Papoz L, Richard JL, Claude JR, Rosselin G. Relationship of plasma insulin level to the incidence of myocardial infarction and coronary heart disease mortality in middle-aged population. Diabetologia. 1980;19:205–210.[Medline] [Order article via Infotrieve]
34. Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentration. Diabetes Care. 1979;2:154–160.[Abstract]
35.
Rönnemaa T, Laakso M, Pyörälä
K, Kallio V, Puukka P. High fasting plasma insulin is an indicator of
coronary heart disease in non-insulin-dependent diabetic
patients and nondiabetic subjects. Arterioscler Thromb. 1991;11:80–90.
36. Badimon JJ, Fuster V, Chesebro JH, Badimon L. Coronary atherosclerosis: a multifactorial disease. Circulation. 1993;87(suppl 3):II-3–II-16.
37. Colwell JA. Vascular thrombosis in type II diabetes. Diabetes. 1993;42:8–11. Editorial.[Medline] [Order article via Infotrieve]
38. Laakso M. Epidemiology of diabetic dyslipidemia. Diabetes Rev. 1995;3:408–422.
39.
Laakso M. Glycemic control and the risk of
coronary heart disease in patients with non-insulin-dependent
diabetes mellitus. Ann Intern Med. 1996;124:127–130.
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Z. T. Bloomgarden European Association for the Study of Diabetes (EASD) 2001 Meeting Diabetes Care, July 1, 2002; 25(7): 1229 - 1236. [Full Text] [PDF]
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 J. Westerbacka, A. Uosukainen, S. Makimattila, A. Schlenzka, and H. Yki-Jarvinen Insulin-Induced Decrease in Large Artery Stiffness Is Impaired in Uncomplicated Type 1 Diabetes Mellitus Hypertension, May 1, 2000; 35(5): 1043 - 1048. [Abstract] [Full Text] [PDF]
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