Carl-David Agardh

Long-term prognosis for diabetic patients with foot ulcers

Abstract. Objective. To evaluate the recurrence of foot ulcers as well as the cumulative amputation and mortality rates in diabetic patients with previous foot ulcers.

Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach?

The purpose of this retrospective study was to evaluate the changes in diabetes‐related lower extremity amputations following the implementation of a multidisciplinary programme for prevention and treatment of diabetic foot ulcers in a 0.2 million population with a 2.4 % prevalence of diabetes. All diabetes‐related primary amputations from toe to hip from 1 January 1982 to 31 December 1993 were included. In 294 diabetic patients, 387 primary major (above the ankle) or minor (through or below the ankle) amputations were performed, constituting 48 % of all lower extremity amputations. The annual number of amputations at all levels decreased from 38 to 21, equalling a decrease of incidence from 19.1 to 9.4/100 000 inhabitants (p = 0.001). The incidence of major amputations decreased by 78% from 16/1 to 3.6/100 000 inhabitants (p<0.001). The absolute number of amputations with a final level below the ankle showed no increase, but their proportion increased from 28 to 53 % (p<0.001) and the reamputation rate decreased from 36 to 22 % (p<0.05) between the first and last 3‐year period. Thus, a substantial long‐term decrease in the incidence of major amputations was seen as well as a decrease in the total incidence of amputations in diabetic patients. Seventy‐one per cent of the amputations were precipitated by a foot ulcer. These findings indicate that a multidisciplinary approach plays an important role to reduce and maintain a low incidence of major amputations in diabetic patients

Long-term prognosis after healed amputation in patients with diabetes

In this prospective study, mortality, rehabilitation, and new amputations on the same or on the contralateral leg were studied in 189 patients with diabetes who had achieved healing of an index amputation. Ninety-three patients had achieved healing after an index minor (below the ankle) and 96 after an index major (above the ankle) amputation, precipitated by a foot ulcer. The healing time was 29 weeks (range, 3–191 weeks) with a minor amputation and 8 weeks (range, 3–104 weeks) with a primary major amputation. The mortality 1, 3, and 5 years after the index amputation was 15%, 38%, and 68%, respectively, and was higher in patients who had achieved healing after major amputation than in patients achieving healing after minor amputation. The rate of new amputations after 1, 3, and 5 years of observation was 14%, 30%, and 49%, respectively. There was no difference among patients with an index minor and those with an index major amputation. The rate of new major amputations was 9%, 13%, and 23%, respectively, and was higher in patients with an index major amputation. Eighty-five percent of new amputations were precipitated by a foot ulcer. Patients living independently before the index amputation returned to living independently more often after a minor than a major amputation (93% versus 61%). One year after the index amputation, 70% of patients who had achieved healing after having a minor amputation and who could walk 1 km or more before amputation had regained this walking capacity, compared with 19% of patients having a major amputation. Seventy percent of patients with an index transtibial amputation who could walk before amputation were fitted with a prosthesis, and 52% were using it regularly. Patients with diabetes who had an index major amputation had a higher mortality, an equal rate of new amputation, and a lower rehabilitation potential than did patients who had an index minor amputation.

Prognostic value of systolic ankle and toe blood pressure levels in outcome of diabetic foot ulcer

The prognostic value of distal blood pressure measurements has been studied in 314 consecutive diabetic patients with foot ulcers. Systolic toe blood pressure was measured with a strain-gauge technique, and ankle pressure was measured with strain-gauge or Doppler techniques. Wound healing was defined as intact skin for at least 6 mo. One hundred ninety-seven patients healed primarily, 77 had amputations, and 40 died before healing had occurred. In 294 of 300 patients, it was possible to measure either ankle or toe pressure. Fourteen patients were not available for pressure measurements. Of these, 10 patients healed primarily, and 4 died before healing occurred. Both ankle and toe pressures were higher (P < .001) among patients who healed without amputation compared with those who underwent amputation or died before healing. No differences were seen in ankle or toe pressure levels among those who had amputations or died. No patient healed primarily with an ankle pressure < 40 mmHg. An upper limit above which amputation was not required could not be defined. Primary healing was achieved in 139 of 164 patients (85%) with a toe pressure level >45 mmHg, whereas 43 of 117 patients (36%; P < .001) healed without amputation when toe pressure was ≤45 mmHg. In conclusion, a combination of ankle and toe pressure measurements is a useful tool to predict primary healing in diabetic foot ulcers.

Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus

The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3 mumols l-1; mean +/- SD, p less than 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6 mumols l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3 mumols l-1; n = 25), and the control subjects (11.0 +/- 3.4 mumols l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels greater than 115 mumols l-1 and/or an albumin:creatinine clearance ratio greater than or equal to 0.02 x 10(-3) (17.0 +/- 5.9 mumols l-1; n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5 mumols l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients.

Direct medical costs for patients with type 2 diabetes in Sweden

Abstract. Henriksson F, Agardh C‐D, Berne C, Bolinder J, Lönnqvist F, Stenström P. Östenson C‐G, Jönsson B (Centre for Health Economics, Stockholm; Department of Endocrinology, University Hospital MAS, Malmö; Department of Internal Medicine, Uppsala University Hospital; Centre for Metabolism and Endocrinology and SmithKline Beecham Pharmaceuticals AB, Karolinska Institute; Diabetes Prevention Unit, Karolinska Hospital, Stockholm, Sweden). Direct medical costs for patients with type 2 diabetes in Sweden. J Intern Med 2000; 248: 387–396.

Cerebral metabolic changes in profound, insulin-induced hypoglycemia, and in the recovery period following glucose administration

Severe hypoglycemia was induced by insulin in lightly anaesthetized (70°o N2O) and artificially ventilated rats. Brain tissue was frozen in situ after spontaneous EEG potentials had disappeared for 5. 10. 15 or 30 min and cerebral cortex concentrations of labile organic phosphates, glycolytic metabolites, ammonia and amino acids were determined. In other experiments, recovery was induced by glucose injection at the end of the period of EEG silence.

Socio‐demographic and psychosocial factors are associated with features of the metabolic syndrome. The Women's Health in the Lund Area (WHILA) study

Aim: The aim was to analyse any associations between socio‐demographic and psychosocial factors and different features of the metabolic syndrome in a geographically well‐defined population of middle‐aged women.

Hypoglycemic brain injury. I. Metabolic and light microscopic findings in rat cerebral cortex during profound insulin-induced hypoglycemia and in the recovery period following glucose administration

SummaryProfound hypoglycemia causing the disappearance of spontaneous EEG activity was induced by insulin in rats. For analysis of cerebral cortical concentrations of labile phosphates, glycolytic metabolites and amino acids, the brain was frozen in situ. For microscopic analysis of the corresponding cerebral cortical areas the brain was fixed by perfusion. Hypoglycemia with an isoelectric EEG for 30 and 60 min caused severe perturbation of the cerebral energy metabolites. After both 30 and 60 min of isoelectric EEG, two microscopically different types of nerve cell injury were seen. Type I injury was characterized by angulated, darkly stained neurons with perineuronal vacuolation, mainly affecting small neurons in cortical layer 3. Type II injured neurons, mainly larger ones in layers 5–6, were slightly swollen with vacuolation or clearing (depending on the histotechnique used) of the peripheral cytoplasm, but had no nuclear changes.Recovery was induced by glucose injection. Improvement in the cerebral energy state occurred during the 30 min recovery period even after 60 min of hypoglycemia. However, the persisting reduction in the size of adenine nucleotide and amino acid pools after 30 or 180 min recovery suggested that some cells remained damaged. In confirmation many type I injured neurons persisted during the recovery suggesting an irreversible injury. The disappearance of virtually all type II injuries indicated reversibility of these histopathological changes.The microscopic changes in hypoglycemia were different from those in anoxia-ischemia suggesting a dissimilar pathogenesis in these states despite the common final pathway of energy failure.

Endogenous substrates utilized by rat brain in severe insulin-induced hypoglycemia

Abstract: Several previous studies have demonstrated that severe hypoglycemia is accompanied by consumption of endogenous brain substrates (glycolytic and citric acid cycle metabolites and free amino acids) and some have shown a loss of structural components as well, notably phospholipids. In the present study, on paralysed and artificially ventilated rats, we measured cerebral oxygen and glucose consumption during 30 min of hypoglycemic coma (defined as hypoglycemia of sufficient severity to cause cessation of spontaneous EEG activity) and calculated the non‐glucose oxygen consumption. In an attempt to estimate the missing substrate we measured tissue concentrations of phospholipids and RNA.