[Sensitive quality indicators stimulate improvement of care]. / Känsliga kvalitetsindikatorer stimulerar till bättre vård.

For the past four years, 52 of the approximately 80 departments of medicine in Sweden have collected data on key indicators of quality of care with regards to acute myocardial infarction, stroke, anticoagulant treatment, and diabetes. The results are analysed centrally, each department being supplied with feedback in the form of overall results, and comparison of its own values with the respective means. Gradual general improvement has been discernible over time, though there is still room for improvement at some departments. There have been isolated instances of manifest changes in indicator values associated with major departmental reorganisation, probably reflecting real deterioration in quality of care. Thus, indicator monitoring would appear a sensitive means of promoting qualitative improvement.

Daytime glibenclamide and bedtime NPH insulin compared to intensive insulin treatment in secondary sulphonylurea failure: a 1-year follow-up.

The aim of this study was to compare the metabolic effects of a combination of daytime glibenclamide and evening NPH insulin with intensive insulin treatment (rapid acting insulin before meals and NPH insulin at bedtime) in patients exhibiting secondary failure to sulphonylurea treatment. Thirty-nine mildly obese NIDDM patients (BMI 25.6 +/- 0.5) were randomized after 6 weeks of intensive insulin treatment to either a combination treatment (CT, n = 20) or continued intensive insulin treatment (IT, n = 19). There were no differences between the two groups in age, diabetes duration, BMI, HbA1c, or basal and glucagon stimulated C-peptide. The patients were followed for 1 year and the findings were analysed on an intent to treat basis. Two patients in the CT group were excluded after 2 and 6 months, respectively, due to unacceptably high postprandial glucose values. There was a significant difference in HbA1c between the CT and IT groups at 6 months (8.2 +/- 0.2, n = 19, vs 6.8 +/- 0.4%, n = 19, p < 0.001)), but not at 12 months (7.8 +/- 0.3, n = 18, vs 7.5 +/- 0.4%, n = 19). After the initial intensive insulin treatment, BMI was constant in the CT group but increased significantly at 6 and 12 months in the IT group. We conclude that both treatments are associated with a marked and long-term improvement of glycaemic control. The intensive insulin treatment leads to a more pronounced weight increase which in the long run might have negative effect on overall metabolic control. Therefore, the combination treatment together with intensified education and dietary advice should be regarded as the initial treatment of choice for oral agent failure in moderately obese NIDDM patients.

Effects of combination therapy with glyburide and insulin on serum lipid levels in NIDDM patients with secondary sulfonylurea failure.

OBJECTIVE: To compare the long-term effect of combined treatment with insulin and glyburide versus insulin alone on serum lipid levels in non-insulin-dependent diabetic (NIDDM) patients with secondary failure to sulfonylurea therapy. RESEARCH DESIGN AND METHODS: The study was a randomized double-blind placebo-controlled parallel trial with a duration of 325 days. The study was conducted at a referral-based endocrinology clinic. Subjects were a sequential sample of 20 patients with NIDDM with failure to respond to glyburide treatment after at least 1 yr of adequate glucose control with this therapy. The patients were randomized to treatment with insulin and glyburide (IG) or insulin and placebo (IP). Insulin was given twice daily to all patients as a mixture of NPH and regular insulins in dosages aiming at optimal glucose control. Glyburide or placebo was taken before breakfast (7 mg) and dinner (3.5 mg). RESULTS: Mean HbA1c decreased from 11.1% (range 9.8-12.9%) before insulin to 9.1% (range 6.8-11.4%) on day 325 (P less than 0.001) in IG patients and from 10.3% (range 8.4-13.3%) to 9.0% (range 6.3-11.8%) (P less than 0.05) in IP patients. In both groups, there was an increase in high-density lipoprotein cholesterol of approximately 20% lasting throughout the study (P less than 0.01). During the first 83 days of the study, there was a decrease in serum cholesterol (P less than 0.01) and serum triglycerides (P less than 0.05) in both groups. All changes in lipid variables were comparable in magnitude and duration in both treatment with insulin and glyburide in NIDDM patients with secondary sulfonylurea failure improves lipid metabolism to a similar degree as insulin therapy alone.

Metabolic effects and clinical value of beet fiber treatment in NIDDM patients.

In the present study a randomized cross-over design was used to determine the clinical usefulness of adding 16 g of beet fiber to the ordinary diet of non-insulin dependent diabetic (NIDDM) out-patients. In addition, fiber effects on the gastrointestinal hormone responses to a standardized test meal were evaluated. The study included five patients treated with diet alone and eight patients treated with diet and sulphonylurea (SU). Beet fiber supplementation resulted in a 10% reduction (P less than 0.01) of serum cholesterol in SU-treated patients. No differences were found for fasting blood glucose, glycated hemoglobin, serum triglycerides or body weight. In the diet-treated patients, fasting plasma somatostatin was elevated during the fiber period. However, postprandial responses of insulin, C-peptide, glucagon, gastric inhibitory peptide and somatostatin were not influenced by an increased fiber intake in any group. All patients experienced mild gastrointestinal discomfort during the fiber period. In view of the limited metabolic benefit of beet fiber treatment we conclude that there is little use for this type of dietary fiber in the routine treatment of patients with NIDDM.

Glucose turnover in hyperthyroid patients with normal glucose tolerance.

To determine the diabetogenic effect(s) of thyroid hormones, we simultaneously measured glucose turnover in six hyperthyroid patients and six normal subjects. All had normal fasting blood glucose concentration and oral glucose tolerance test values. We determined hepatic total glucose output (HTGO) and total glucose phosphorylation with [2-3H]glucose and hepatic glucose production (HGP) and irreversible glucose uptake using [6-3H]glucose. The difference between the two turnover rates indicates the extent of hepatic glucose cycling (glucose in equilibrium glucose-6-phosphate). Measurements were made both in the postabsorptive steady state and during a 2-h glucose infusion (11.1 mumol/kg.min). The postabsorptive HTGO and total glucose phosphorylation were increased in the hyperthyroid patients [13.5 +/- 0.8 (+/- SE) vs. 11.3 +/- 0.4 mumol/kg.min; P less than 0.05]. HGP and irreversible glucose uptake also were slightly but not significantly higher. During the glucose infusion, HTGO and HGP were less suppressed in the hyperthyroid patients than in the normal subjects, while the increments in peripheral glucose uptake were normal. In hyperthyroidism, glucose cycling was increased both postabsorptively (2.35 +/- 0.27 vs. 1.17 +/- 0.25 mumol/kg.min; P less than 0.025) and during glucose infusion (2.57 +/- 0.34 vs. 1.31 +/- 0.35 mumol/kg.min; P less than 0.05). We conclude that increases in HTGO and HGP are important features of hyperthyroidism, especially during glucose infusion. The increase in GC indicates increased activities of both glucokinase and glucose-6-phosphatase. The diabetogenic effect of hyperthyroidism, as revealed most markedly by [2-3H]glucose, could be accounted for by augmented glucose production, possibly due to increased glucose-6-phosphatase activity.

Mild type II diabetes markedly increases glucose cycling in the postabsorptive state and during glucose infusion irrespective of obesity.

Glucose cycling (GC; G in equilibrium G6P) equals 14% of glucose production in postabsorptive man. Our aim was to determine glucose cycling in six lean and six overweight mild type II diabetics (fasting glycemia: 139 +/- 10 and 152 +/- 7 mg/dl), in postabsorptive state (PA) and during glucose infusion (2 mg/kg per min). 14 control subjects were weight and age matched. GC is a function of the enzyme that catalyzes the reaction opposite the net flux and is the difference between hepatic total glucose output (HTGO) (2-[3H]glucose) and hepatic glucose production (HGP) (6-[3H]-glucose). Postabsorptively, GC is a function of glucokinase. With glucose infusion the flux is reversed (net glucose uptake), and GC is a function of glucose 6-phosphatase. In PA, GC was increased by 100% in lean (from 0.25 +/- 0.07 to 0.43 +/- .08 mg/kg per min) and obese (from 0.22 +/- 0.05 to 0.50 +/- 0.07) diabetics. HGP and HTGO increased in lean and obese diabetics by 41 and 33%. Glucose infusion suppressed apparent phosphatase activity and gluconeogenesis much less in diabetics than controls, resulting in marked enhancement (400%) in HTGO and HGP, GC remained increased by 100%. Although the absolute responses of C-peptide and insulin were comparable to those of control subjects, they were inappropriate for hyperglycemia. Peripheral insulin resistance relates to decreased metabolic glucose clearance (MCR) and inadequate increase of uptake during glucose infusion. We conclude that increases in HGP and HTGO and a decrease of MCR are characteristic features of mild type II diabetes and are more pronounced during glucose infusion. There is also an increase in hepatic GC, a stopgap that controls changes from glucose production to uptake. Postabsorptively, this limits the increase of HGP and glycemia. In contrast, during glucose infusion, increased GC decreases hepatic glucose uptake and thus contributes to hyperglycemia. Obesity per se did not affect GC. An increase in glucose cycling and turnover indicate hepatic insulin resistance that is observed in addition to peripheral resistance. It is hypothesized that in pathogenesis of type II diabetes, augmented activity of glucose-6-phosphatase and kinase may be of importance.

Glyburide decreases insulin requirement, increases beta-cell response to mixed meal, and does not affect insulin sensitivity: effects of short- and long-term combined treatment in secondary failure to sulfonylurea.

In 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea, a double-blind randomized study was performed comparing two regimes: insulin plus placebo (IP) and insulin plus glyburide (IG). The protocol included two hospitalization periods (days 1-18 and 78-85) and follow-up at the outpatient clinic for 325 days. The metabolic control was kept as tight as possible. The subjects underwent normoglycemic clamp studies and meal tests with determination of insulin, C-peptide, glucagon, somatostatin, and gastric inhibitory polypeptide in plasma. On IG, they demonstrated marked and long-lasting improvement of metabolic control: HbA1c decreased from 11.1 +/- 0.3% on day 3 to 8.3 +/- 0.4% (P less than .001) on day 78 and 9.1 +/- 0.5% (P less than .001) on day 325. In subjects on IP, the corresponding values were 10.3 +/- 0.5, 8.4 +/- 0.4 (P less than .001), and 8.9 +/- 0.5% (P less than .05). Body weight increased by 6.0 +/- 1.5 kg (P less than .005) on IG and 2.9 +/- 2.1 kg (NS) on IP. The daily insulin requirement decreased on IG from 62.5 +/- 12.9 U/day on day 7 to 33.5 +/- 8.8 U/day on day 83 and 34.6 +/- 8.9 U/day on day 325. On IP the insulin requirement was almost constant: 62.0 +/- 10.7 U/day on day 7, 55.5 +/- 7.7 U/day on day 83, and 54.7 +/- 7.9 U/day on day 325. Insulin sensitivity measured with the hyperinsulinemic clamp (plasma insulin approximately equal to 130 microU/ml) was similar on IP and IG at the initiation of the study and was unchanged on days 18 and 85. A key observation of this study, although the mechanism is unclear, is that isoglycemic-meal-related insulin requirement was diminished by insulin treatment, indicating improvement of meal-related insulin sensitivity. Glyburide increased basal and meal-but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release. We conclude that in NIDDM, IG regime promptly and continuously decreased insulin requirement and improved metabolic control. This effect is, at least during the first 3 mo, mainly due to enhanced insulin secretion. IG and IP treatment had no effect on insulin sensitivity during hyperinsulinemic-normoglycemic clamp, whereas meal-related insulin sensitivity was augmented.

Glucose and fructose 6-phosphate cycle in humans.

We have determined the rate of glucose cycling by comparing turnovers of [2-3H]- and [6-3H]glucose under basal conditions and during a glucose infusion. Moreover, the activity of the fructose 6-phosphate cycle was assessed by comparing [3-3H]- and [6-3H]glucose. The study included eight lean subjects with normal glucose tolerance. They participated in two randomly performed investigations. In one experiment [2-3H]- and [6-3H]glucose were given simultaneously, while in the other only [3-3H]glucose was given. The basal rate of glucose cycling was 0.32 +/- 0.08 mg X kg-1 X min-1 or 17% of basal glucose production (P less than 0.005). During glucose infusion the activity of endogenous glucose cycling did not change but since glucose production was suppressed it amounted to 130% of glucose production. The basal fructose 6-phosphate cycle could be detected only in three subjects and was suppressed during glucose infusion. In conclusion, the glucose cycle is active in healthy humans both in basal conditions and during moderate hyperglycemia. In some subjects, the fructose 6-phosphate cycle also appears to be active. Thus it is preferable to use [6-3H]glucose rather than [3-3H]glucose when measuring glucose production and particularly when assessing glucose cycle.

Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance.

To characterize the diabetogenic effects of growth hormone, we simultaneously measured glucose turnover with 2-3H- and 6-3H-glucose in six acromegalic patients with normal fasting blood glucose and oral glucose tolerance tests. Eight healthy volunteers served as controls. All subjects were studied under both basal conditions and during glucose infusion (2 mg X kg-1 X min-1). We determined true glucose production and irreversible glucose uptake using 6-3H-glucose and glucose cycling (difference between 2-3H- and 6-3H-glucose). After an overnight fast, glucose production was higher than normal in the acromegalic patients (2.18 +/- 0.15 vs 1.85 +/- 0.03 mg X kg-1 X min-1, p less than 0.05) despite hyperinsulinaemia. The metabolic clearance rate was normal. During the glucose infusion, glucose production was not suppressed as effectively in the acromegalic patients as in controls nor was glucose uptake augmented, while metabolic clearance rate was decreased. In acromegaly, basal glucose cycling was increased (0.44 +/- 0.08 vs 0.25 +/- 0.07 mg X kg-1 X min-1, p less than 0.05). Furthermore cycling of endogenous glucose measured during glucose infusion was also augmented (0.41 +/- 0.05 vs 0.24 +/- 0.05 mg X kg-1 X min-1, p less than 0.05). Hence the increase of glucose cycling (70%) was much more pronounced than that of glucose production (17%). In conclusion, small defects in glucose metabolism in acromegaly can be detected with sensitive tracer methods. These derangements are confined to the liver under fasting conditions, but are of both hepatic and extrahepatic origin during glucose loading.

Glucose tolerance in patients undergoing continuous ambulatory peritoneal dialysis.

The effects of continuous ambulatory peritoneal dialysis (CAPD) on glucose tolerance and serum immunoreactive insulin and glucagon responses to oral glucose over the first year of therapy were studied in 13 uremic patients. Oral glucose tolerance tests were performed before treatment started, and again after 3 and 12 months on CAPD. Before CAPD, the patients showed decreased glucose tolerance. However, neither fasting blood glucose and serum insulin and glucagon levels nor the insulin and glucagon levels during the tests were significantly different from results obtained in 13 healthy controls. During CAPD, the mean intraperitoneal supply of glucose from the dialysates varied between 121 and 245 g/day and did not change during the study period. Glucose tolerance and hormone responses to glucose did not change during the study period. No patient developed manifest diabetes mellitus. We conclude that glucose intolerance in uremia persists during CAPD, but despite the continuous peritoneal absorption of 100-200 g of glucose during CAPD, the treatment had no effect on glucose tolerance and insulin secretory response.

Nutritive toe skin capillaries in middle-aged patients with diabetes mellitus.

Vital capillary microscopy was employed in a study of the toe dorsum capillaries in 92 middle-aged diabetics and 96 controls of similar age and sex distribution. As a general finding most vision fields in the same toe showed an almost identical capillary pattern. In 17% of the toes in the controls compared to about 35% of the toes in the patients the capillaries were dilated more than 3 times. Such findings were unrelated to blood glucose control and a number of metabolic variables. In the patients with non-insulin dependent diabetes an abnormal capillary pattern was particularly common in patients with evidence of obstructive arterial disease. Such a relationship was not observed in patients with insulin-dependent diabetes in whom changes in the capillary pattern to a higher extent may be related to other mechanisms such as neuropathy.

Effects of a rice-rich versus a potato-rich diet on glucose, lipoprotein, and cholesterol metabolism in noninsulin-dependent diabetics.

Previous reports have demonstrated that noninsulin-dependent diabetes mellitus often is associated with hypertriglyceridemia linked to hyperinsulinemia and enhanced cholesterogenesis. Studies with single meals have indicated that rice as compared to potato results in a less pronounced blood glucose and insulin response. These findings initiated the current study in which eight middle-aged patients with adult-onset, noninsulin-dependent diabetes were fed a standardized diet with potato or rice as the major carbohydrate source. Blood glucose control was the same during both dietary periods. When rice was the major carbohydrate source the very low density lipoprotein triglycerides decreased in six patients and the formation of bile acid, especially that of cholic acid, showed a significant drop. The results further underline a link between lipoprotein and bile acid metabolism.

Vital capillary microscopy for assessment of skin viability and microangiopathy in patients with diabetes mellitus.

Vital capillaroscopy is useful in clinical practice to study the nutritional skin capillaries and for evaluating the risk for skin necrosis in patients with peripheral ischemia. This method is especially valuable in the investigation of patients with diabetes mellitus (DM) in whom the arterial inflow to the foot can be almost normal despite the development of skin necrosis due to impaired nutritional circulation. When the capillary morphology in the feet of asymptomatic diabetic patients was investigated, significantly more areas with widely dilated capillaries were present both in insulin and tablet treated patients compared to controls. By using dynamic capillaroscopy the flow velocity in skin capillaries can be determined under physiological conditions. Fourteen diabetic patients were compared with matched non-diabetic controls. The capillary blood flow during resting conditions was equal in the two groups but a delay in the postocclusive reactive hyperemia response was seen in the diabetic patients. The reason for this may be a vasomotor dysfunction in the precapillary arterioles or an increased blood viscosity. Further studies using dynamic vital capillaroscopy may improve our knowledge of the complex mechanisms responsible for diabetic microangiopathy.

Effects of a formalized diabetes education.

A previous study of patients attending a diabetic out-patient clinic indicated that their metabolic control was inadequate and their knowledge of diabetes and diabetes management was generally low. In an attempt to improve the situation, we organized a five-day education programme comprising formal lessons about diabetes, diet and nutrition. Altogether 83 patients completed the course. The test scores before and one year after the course indicated that the patients' knowledge had improved. Metabolic control, however, was essentially unchanged at the follow-up.

Metabolic effects of continuous ambulatory peritoneal dialysis.

Prospective studies concerning protein, carbohydrate, and lipid metabolism were performed in 19 CAPD patients. After 2-4 months on CAPD the mean nitrogen balance was positive (3.14 +/- 1.98 g N/day) and was correlated with protein and energy intake as well as with the increase in body weight. Plasma free amino acid concentrations were normal, but the tyrosine/phenylalanine ratio was decreased compared with healthy subjects. In spite of the excessive glucose load, there was no further deterioration in glucose tolerance. Serum concentrations of TG and CHOL were increased due to a rise of VLDL-TG and VLDL-CHOL.

Knowledge of diabetes mellitus, diets and nutrition in diabetic patients.

A multiple choice questionnaire was used to test the level of knowledge abut diabetes mellitus and diet-nutrition in diabetic patients (n = 317), non-diabetic patients (n = 70), nursing personnel (n = 53) and third-year medical students (n = 43). The results concerning diabetes were better than those for diet-nutrition. A score of greater than or equal to 80% in diet-nutrition was considered necessary for proper management of the diet at home. This level was reached by 84% of the students, 26% of the nursing personnel, 29% of the insulin-treated diabetics (n = 178, 9% of the tablet-treated diabetics (n = 124) and 4% of the non-diabetic patients. It was concluded that the piecemeal instruction system used to teach the diabetic patients is inefficient and should be replaced by a formal educational program integrated into the patient care system. The level of knowledge among nursing personnel needs to be improved.