Else Marie Damsgaard

Microalbuminuria as predictor of increased mortality in elderly people.

OBJECTIVE--Correlation of the urinary albumin excretion rate and the risk of death among elderly subjects. DESIGN--216 Subjects aged 60-74 whose urinary albumin excretion rate had been determined were followed up 62-83 months later. SETTING--Municipality of Fredericia, Denmark. SUBJECTS--223 People who had been selected as control subjects for diabetics found during a systematic screening for diabetes of all people aged 60-74 living in the municipality of Fredericia, Denmark. Of these subjects, 216 had an extensive clinical and biochemical examination within a few weeks of selection. MAIN OUTCOME MEASURE--Death. RESULTS--The median urinary albumin excretion rate was 7.52 micrograms/min. Eight of those with a rate below the median died compared with 23 with a rate equal to or greater than the median (p = 0.0078). The median albumin excretion rate in the 31 who died was 15.00 micrograms/min. Cardiovascular disease was the most common cause of death in both groups. A multivariate regression analysis of survival data was performed using the proportional hazards model. Besides albumin excretion rate, male sex, serum creatinine concentration, and hypertension were found to be of prognostic value. CONCLUSIONS--The association between the albumin excretion rate and mortality that has been described in recent years in patients with diabetes mellitus may be present in elderly people in general, even when other known risk factors are taken into account.

Blood Pressure Elevation Versus Abnormal Albuminuria in the Genesis and Prediction of Renal Disease in Diabetes

A number of risk factors associated with the development of diabetic nephropathy has been described, such as elevated blood pressure, poor metabolic control, hyperlipidemia, and smoking. Abnormal albuminuria also is associated with progression of renal disease, but has until recently been considered principally a marker of disease activity rather than a risk factor. This article discusses the role of elevated blood pressure versus abnormal albuminuria in a genesis and prediction of renal disease in diabetes. Controversy exists regarding parental disposition to hypertension and early blood pressure elevation in the course of diabetes, but all studies agree that elevated blood pressure—in the presence of abnormal albuminuria—constitutes a risk factor. Because abnormal albuminuria is associated with progression disease, it may itself be a risk factor because increased macromolecular traffic over the glomerular membrane may produce glomerulopathy. Problems related to blood pressure measurement are important, and 24-h recordings of blood pressure may be recommended in some situations. Regarding renal structure, preliminary results suggest that structural lesions precede blood pressure elevation. The solid end point for evaluation of renal disease progression is the fall rate of GFR, with abnormal albuminuria as an intermediate end point, also in drug trials. Abnormal albuminuria may constitute a new indication for antihypertensive treatment, being, as it is, a clear indicator of organ damage, whereas elevated blood pressure with normal AER may not increase risk substantially.

Prevalence and prediction of silent ischaemia in diabetes mellitus: a population-based study

OBJECTIVES The aim of the study was to estimate the prevalence of silent ischaemia in diabetic subjects in the population, to compare the prevalence of silent ischaemia in diabetics and non-diabetics and to attempt to predict the presence of silent ischaemia in diabetic subjects. METHODS A random sample of 120 users of insulin and 120 users of oral hypoglycaemic agents aged 40-75 years living in the Danish municipality of Horsens were asked to participate in the study. Corresponding to the youngest half of the sample two non-diabetic controls were randomly selected from the Central Population Register. ST-depression of horizontal or descending character of at least 0.1 mV measured 80 ms after the J-point on either exercise ECG or Holter ECG was considered indicative of myocardial ischaemia. Angina pectoris was considered present if the Rose questionnaire was positive, or chest pain was registered simultaneously with ECG evidence of ischaemia. Individuals with ischaemia, but without angina pectoris, were defined as persons with silent ischaemia. RESULTS Seventy-four percent of the invited group were included. The observed prevalence of silent ischaemia in diabetics was 13.5% (95% CI = 8.5-19.8%). No association was found between silent ischaemia and gender (P = 0.83) or diabetes type (P = 0.67). In the group of diabetics who had controls, the prevalence was 11.4%, and among the controls the prevalence was 6.4% (OR = 1.87, one-sided P = 0.079). Systolic blood pressure was highly predictive of silent ischaemia in the diabetic subjects (P = 0.005). No predictive value could be shown for other variables. CONCLUSION This is the first population-based study of silent ischaemia in diabetes. The prevalence of silent ischaemia in diabetic subjects was 13.5%. The frequency of silent ischaemia did not differ significantly between diabetics and non-diabetics. Systolic blood pressure was predictive of silent ischaemia in diabetes.

Predischarge maximal exercise test identifies risk for cardiac death in patients with acute myocardial infarction

A maximal exercise test was performed in 54 patients with acute myocardial infarction (AMI) before discharge and in 49 age-matched control subjects. The long-term prognosis was assessed after an average follow-up of 7.6 years in AMI patients and 5.8 years in control subjects. The maximal work capacity and systolic blood pressure increase in AMI patients was 59% that of control subjects (p less than 0.001). Seventeen AMI patients had significant ST-segment shifts, 13 with ST depression and 4 with ST elevation. In AMI patients experiencing a cardiac death during follow-up the maximal work capacity and systolic blood pressure increase were significantly lower than in survivors and those who died from noncardiac reasons (p less than 0.01; p less than 0.05), with no difference between these groups in the number of patients with ST-segment shifts. The average maximal work capacity of control subjects was 143 watts. A maximal work capacity half this (less than or equal to 72 watts) predicted long-term mortality in AMI patients (p less than 0.001). In addition a low increase in systolic blood pressure (less than 30 mm Hg) also predicted long-term mortality (p less than 0.005), whereas ST shifts were of no significant value. In this study maximal work capacity turned out to be the best single exercise variable for identifying groups of AMI patients with very low and relative high risk of cardiac death. When all 3 exercise variables were combined, the predischarge maximal exercise test was of great value in identifying AMI patients at low risk for cardiac death (predictive value of a negative test: 95%).

Reproducibility of beta-cell function estimates in non-insulin-dependent diabetes mellitus.

We evaluated the reproducibility of different estimates of endogenous insulin secretion in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM). Fasting blood glucose concentration was similar on the 2 days of study. The coefficients of variation of fasting plasma C-peptide, plasma Cpeptide 6 min after the injection of 1 mg i.v. glucagon, and the increment in plasma C-peptide after glucagon were 16.0, 14.8 and 24.1%, respectively. The coefficients of variation of the corresponding plasma insulin values were 19.2, 24.8, and 34.8%, respectively. The coefficient of variation of 24-h urinary C-peptide excretion was 22.1%. Because fasting plasma C-peptide correlated closely with plasma C-peptide 6 min after giucagon (test 1: r = .70, P < .01; test 2: r = .76, P < .01), it seems that these two values can be used equally well as assessment of (3-cell function in NIDDM. In conclusion, fasting plasma insulin, fasting plasma C-peptide, and plasma C-peptide 6 min after glucagon stimulation showed a similar and acceptable degree of reproducibility. Plasma insulin 6 min after glucagon and increments in plasma insulin and C-peptide, as well as urinary C-peptide, seem to be less reproducible.

Prevalence of Fasting Hyperglycemia and Known Non-Insulin-Dependent Diabetes Mellitus Classified by Plasma C-Peptide: Fredericia Survey of Subjects 60–74 Yr Old

A Danish population of 5699 individuals (60–74 yr old) was screened by fasting blood glucose (FBG) and interviewed about known diabetes. The distribution of FBG in individuals not known to have diabetes showed no sex difference or significant variation with age. Fasting hyperglycemia (FH), defined as FBG ≥ 7 mM in subjects without a history of diabetes, was found in 1.7% of men and women. Known diabetes (KD) had a prevalence of 3.9 and 5.0% in men and women, respectively. The prevalence rates of FH and KD increased significantly with age. In the two subgroups, plasma C-peptide was measured after overnight fasting and subsequently 6 min after an intravenous injection of glucagon. Based on the distribution of the C-peptide concentrations in non-insulin-treated KD subjects, lower limits for non-insulin-dependent diabetes mellitus (NIDDM) of 0.30 pmol/ml for fasting C-peptide and 0.60 pmol/ml for stimulated C-peptide were arbitrarily chosen. According to these cutoff points, only 38.5% of KD subjects treated with insulin had insulin-dependent diabetes mellitus, corresponding to 9.3% of all KD subjects. After exclusion of these patients, the prevalence of recognized NIDDM was 3.5% in men and 4.5% in women. All FH subjects except one had C-peptide values in the NIDDM interval. A close agreement between fasting and glucagon-stimulated C-peptide was seen. In epidemiological studies with an expected high prevalence of NIDDM, we propose to use fasting C-peptide for classification of patients with insulin-treated diabetes.

A Geriatric Multidisciplinary and Tailor-Made Hospital-At-Home Method in Nursing Home Residents With Hip Fracture:

Introduction: Nursing home residents represent a large proportion of patients hospitalized with hip fracture. Generally, residents do not achieve the same physical ability level as before their fracture and have an increased risk of death within few days after discharge. This study aims to compare 2 new approaches to geriatric intervention in residents with hip fracture. Materials and Methods: In nursing home residents aged 65 or older with hip fracture, 85 received a newly developed standardized rehabilitation intervention undertaken by the geriatric orthopedic team (GO team) from December 1, 2006 to November 30, 2007. This standardized method was compared with a further developed tailor-made intervention method performed by the GO team in 153 residents from February 1, 2008 to January 31, 2010. Both the interventions began at hospital admission and until 30 days after surgery. Outcomes were length of hospital stay (LOS), difference in physical ability, 90-day acute readmission, 30-day mortality, and 90-day mortality. Results: The tailor-made intervention method reduced the readmission rate (14% vs 26%) compared with the standardized intervention method (odds ratio [OR] = 0.47 [95% confidence interval [CI]: 0.23, 0.94]). Tailor-made intervention reduced 30-day mortality (8% vs 19%) compared with standardized intervention (OR = 0.42 [95% CI: 0.18, 0.97]). Improving 90-day survival could not be demonstrated (81% vs 73%; OR = 0.72 [95% CI: 0.37, 1.40]). Median LOS was 2 days in both the groups. A total of 7 follow-up visits were performed with tailor-made intervention versus 3 visits with standardized intervention. In both the groups, the physical ability decreased significantly within the first 30 postoperative days, with no difference between groups (β = 1.01 [95% CI: 0.82, 1.24]).Conclusion: A multidisciplinary and tailor-made geriatric intervention in nursing home residents has a positive effect on readmission rate and short-term mortality. Still, it is not obvious which part of the tailor-made intervention is most crucial.

Over-mortality as related to age and gender in patients with established non-insulin-dependent diabetes mellitus.

In 1981-1982, 5699 persons representing 92.9% of the total population aged 60-74 years living in Fredericia, Denmark, were interviewed about a possible history of diabetes and had a fasting blood glucose measured. A total of 236 gave a positive history of diabetes; 88 had one fasting blood glucose of 7 mmol/L or more. For each of these probands, an age- and gender-matched control person with normal fasting blood glucose and no history of diabetes was selected randomly. Of the 236, 91.5% had NIDDM as judged by glucagon-stimulated C-peptide tests. At the end of December 1995, the participants were traced through the National Register and their status (alive or dead) was determined. The date of death was confirmed. The median observation time from screening and inclusion in the study till death or the end of the observation period in December 1995 was 12.81 years, the maximum was 14.91, and the 25th and 75th percentile values were 6.36 and 13.94 years, respectively. At the end of 1995, 165 (74.4%) of 228 persons with known diabetes at the time of ascertainment had died opposed to 90 (40.4%) of the 223 nondiabetic control persons. The difference is statistically highly significant (p < 0.00001, log-rank test). Within the first 5 years of observation, 42.9% of diabetic men died and only 22.5% of non-diabetic men. This percentage of deaths in diabetic men was found already in the 60-64 year age interval (46.2%). The mortality rate for the non-diabetic population seems to increase later. After 13 years of observation, 74 (81.3%) of 91 men with known diabetes had died, in the age-matched control men, 50 (56.2%) of 89 (p = 0.00006). Ninety-one (66.4%) of 137 diabetic women had died: 40 (29.9%) of 134 control women (p < 0.00001). The difference between mortality in diabetic men and women, and between nondiabetic men and women is highly significant (p = 0.00285 and 0.00001, respectively). The over-mortality of established diabetic persons decreases with age. In the age group 60-74 years, the over-mortality is about 2.5 without gender difference.

The Diurnal Variation in Blood Pressure should be Calculated from Individually Defined Day and Night Times

The aim of this study was to compare the nocturnal fall in BP parameters calculated from individually defined periods of day and night to values computed from collectively fixed day/night definitions. Day and night periods were defined according to 3 different methods: (i) the individually defined time of getting up and going to bed obtained from participant diaries (MethodIND); (ii) the mean time of rising and retiring in the group (MethodMEAN); and (iii) a daytime period from 07.00-22.00 h as recommended by The Scientific Committee (Method722). The ambulatory BP was recorded every 30 min over 24 h. One hundred and eighty-seven persons aged 40-66 years participated. With MethodIND, the BP load, systolic, diastolic and mean BPs were higher in the daytime and lower in the night-time compared to the results using Method722 and MethodMEAN. The nocturnal BP fall using MethodIND was larger than the fall calculated from every possible fixed division in the period from 3 h before till 3 h after the group mean time of getting up and going to bed (p < 0.001). The lowest frequency of non-dipping, defined as a nightly fall in systolic and diastolic BP below 10%, was observed using MethodIND (10%). Compared to MethodIND, 11% were misclassified as non-dippers by Method722 and 8% by MethodMEAN. We conclude that the diurnal blood pressure variation based on individually defined periods of day and night is larger than the variation based on any collectively fixed day/night definition. It is recommended that assessment of the nocturnal change in BP be based on individually defined periods of day and night.

Acute Actions of Sulfonylurea Drugs During Long-Term Treatment of NIDDM

The acute effect of sulfonylurea drugs during long-term treatment was evaluated in two separate studies. In the first study, the levels of plasma glucose, insulin, and C-peptide were measured after intake of 10 mg glyburide alone or together with a standardized mixed meal in 10 non-insulin-dependent diabetes mellitus (NIDDM) patients treated with 10–20 mg glyburide/day for >2 yr. There was no acute effect of glyburide on the insulin and C-peptide responses to the meal or during continued fasting, indicating the absence of an acute insulinotropic action of glyburide during chronic treatment. The glucose increase after the meal was also unchanged, but a significant glucose reduction was found after glyburide intake during continued fasting, suggesting a sustained acute extrapancreatic (hepatic) effect. In the second study, the diurnal glycemic excursions in 8 NIDDM patients chronically and continuously (24 h/day) exposed to glipizide (2.5–7.5 mg 3 times/day) were similar when the drug was taken 30 min before each of the three main meals and when taken immediately before the meals. It is concluded that there is no acute insulinotropic action of sulfonylurea drugs during chronic continuous exposure, whereas an acute extrapancreatic action may prevail. During such exposure, there seems to be no clinical benefit in taking a sulfonylurea 30 min before rather than at the start of a meal.