Tight Blood Glucose Control Research Articles

Exploding type II

The number of people worldwide with diabetes mellitus is likely to double in the next 10 years (estimated to be 221 million people). The explosion of type II diabetes relates to three linked factors--increasing prevalence of obesity, declining physical activity, and a genetic predisposition. Inheriting a metabolic profile that enhances survival through the reproductive years may be detrimental to well-being in times of plentiful food and sedentary existence. The obesity prevalence figures for England and Wales cause further alarm, with the prevalence in adult men (defined as a BMI, >30 kg/m 2) rising to 14% and in adult women to 17%. In North America, the American Heart Association has upgraded obesity from a contributing to a major risk factor for coronary heart disease in recognition of the associated high rates of morbidity and mortality. The modified diagnostic criteria for diabetes, which have been adopted by the American Diabetes Association and are proposed by the WHO, continue to cause contention. In particular, lowering the fasting plasma from 7.8 mmol/L to 7 mmol/L and the place of the oral glucose tolerance test remain controversial. The proposed criteria appear logical and practical for screening at-risk subjects, but correlate poorly with the previous adopted criteria for diabetes. Moreover, they may significantly alter both the incidence and overall prevalence of the disease. The findings from the UK Prospective Diabetes Study, where the entry criterion was a fasting plasma glucose of 6 retool/L, provide evidence for the effectiveness of strategies for prevention of the complications of type II diabetes. Tight blood-glucose control, achieved through diet, oral hypoglycaemic agents, or insulin, results in a significant reduction in the risk of microvascular complications and does not have an adverse effect on the cardiovascular system--the latter is important given the concerns raised by the University Group Diabetes Programme in the 1970s. Interestingly, metformin proves similarly successful when used as a single agent but is less beneficial when combined with a sulphonylurea: the reasons for this remain unexplained. The benefits f rom long-term strict blood-pressure control, irrespective of the anti-hypertensive treatment used, are impressive, with reductions in all diabetesrelated endpoints, including death, and macrovascular and microvascular disease. However, the inevitable rise in glycosylated HbAlc witnessed throughout the study period, despite strict glycaemic control (figure), emphasises the need for a better understanding of the pathogenesis of type II diabetes in susceptible individuals.

Measurement of glucose in diabetic subjects using noninvasive transdermal extraction

Results from the Diabetes Care and Complications Trial show that tight blood glucose control significantly reduces the long-term complications of diabetes mellitus. In that study, frequent self-testing of glucose and insulin administration resulted in a significant reduction in long-term complications. This protocol, however, also resulted in a threefold increase in the frequency of hypoglycaemic incidents. Currently, self-testing requires a drop of blood for each measurement. The pain and inconvenience of self-testing, along with the fear and danger of hypoglycaemia has led to poor patient acceptance of a tight control regimen, despite the clear long-term advantages. A continuously worn, noninvasive method to periodically measure glucose would provide a convenient and comfortable means of frequent self-testing. A continuously worn device could also alert the user of low glucose levels, thereby reducing the incidence of hypoglycaemia. Guy et al. demonstrated a noninvasive method to transport glucose through the skin using low-level electrical current. To provide a quantitative measurement, the flux of glucose extracted across the skin must correlate with serum glucose in a predictive manner. The results presented here show a quantitative relationship between serum and transdermally extracted glucose in diabetics.

Intensive insulin therapy in insulin-dependent diabetes mellitus, the results of the diabetes control and complications trial

Long term complications are the first causes of mortality and morbidity in diabetic patients. In Europe, many diabetologists speculated for a long time that a tight blood glucose control was the best way to avoid these complications, but without any complete evidence. In 1993, the results of the Diabetes Control and Complications Trial (DCCT), the first controlled, randomized, long term trial designed to study the link between metabolic control and complications in a large cohort of patients, has confirmed this hypothesis: in insulin-dependent diabetes mellitus, intensive insulin-therapy, as compared with conventional therapy, significantly reduces the risk of developing microvascular and neuropathic complications. Nevertheless, in some patients, the risk of hypoglycemia may outweight the benefit of intensive insulin therapy, and the results of the DCCT raises some questions about indications, the risk/benefit ratio and the cost/benefit ratio of intensive treatment.

Application of computers in diabetes carea review. I. Computers for data collection and interpretation

The paper reviews the contribution of information technology (IT) to diabetes care. An appraisal of this topic with respect to insulin-dependent (type 1) diabetic patients is carried out in view of the landmark findings of the Diabetes Control and Complications Trial (DCCT) which has demonstrated that maintaining tight blood glucose control can delay the onset and slow the progression of the later life complications of diabetes. The review starts with the clinical background and the main features of the control schema in which diabetic patients receive insulin therapy. An overview is then provided of recent IT initiatives in diabetes care, and the application of IT techniques to assist in the diagnosis and characterization of patients with diabetes mellitus is considered. The role of IT approaches for short-term glycaemic control is discussed and the utilization of computers for collecting, viewing and interpreting home monitoring blood glucose data is reviewed; both quantitative and qualitative techniques being considered. In the second paper the role of decision support tools for planning insulin therapy using clinical algorithms, hand-held devices, knowledge-based approaches, telemedicine techniques and interactive simulations is reviewed, and the validation and clinical evaluation of these tools is discussed. The likely impact of the routine clinical application of implantable/non-invasive blood glucose monitoring devices is also considered. Finally, the application of computers as teaching tools is reviewed and the ways in which such educational approaches might be applied for disseminating the benefits of the DCCT trial more widely are discussed.

Peripheral arterial disease in the patient with diabetes mellitus. Can we make a difference?

The results of the Diabetes Control and Complications Trial demonstrated that intensive blood glucose regulation decreased the onset and progression of microvascular complications in persons with insulin-dependent diabetes mellitus [ 11. Diabetes is also a major risk factor for atherosclerotic cardiovascular disease [2,3] including peripheral arterial disease (PAD) [4,5]. In persons with non-insulin-dependent diabetes mellitus (NIDDM), the degree of glycemic control is not well correlated with the presence or severity of PAD [6]. In contrast, the associated risk factors of smoking and hyperlipidemia correlate strongly with atherosclerotic disease severity [6,7]. Therefore, it is not yet known if tight blood glucose control will prevent macrovascular complications in persons with diabetes. In fact, it has been suggested that intensive insulin treatment in patients with NIDDM may actually worsen the development of macrovascular disease [8]. Peripheral arterial disease is very common, with a cumulative incidence as high as 45% after 20 years duration of diabetes mellitus [9]. Most of these patients are asymptomatic for PAD, which may lead to a particularly pernicious sequence of events. Until the patient develops symptoms re-

Glycated protein update: implications of recent studies, including the diabetes control and complications trial

On the basis of the results of the Diabetes Control and Complications Trial (DCCT), the American Diabetes Association (ADA) now recommends tight control of blood glucose to near-normal concentrations as the primary goal for most eligible insulin-dependent diabetic patients. In the DCCT, intensive therapeutic intervention was based on frequent self-monitoring of blood glucose and monthly measurements of glycohemoglobin. The importance of glycohemoglobin assessments serves to highlight the present inadequacies in laboratory measurements of this analyte, which hinders wide implementation of the ADA recommendations. Clinical interventions aimed at achieving the DCCT's published therapeutic goals may place patients at a significantly increased risk for life-threatening hypoglycemia, if the therapy is based on nonstandardized laboratory results. Clinical laboratories will now be under increasing pressure to provide reproducible, standardized measurements of glycohemoglobin, a goal that recent research has shown to be realistic, if widespread interlaboratory calibration is adopted. Finally, recent advances in measuring glycated serum proteins appear to warrant reevaluation of such assays during future intensive therapy trials, as potentially important tools for fine-tuning tight blood glucose control.

Commentary and translation: 1994 nutrition recommendations for diabetes

Commentary and translation: 1994 nutrition recommendations for diabetes

Hypoglycaemia in pregnancy

Normally there is a very close relationship between maternal and fetal glucose concentrations during both early and late gestation. Maternal hypoglycaemia during pregnancy will therefore not only affect the mother herself but also the conceptus. As can be judged from the literature, acute hypoglycaemic episodes are only rarely seen in non-diabetic pregnancies. In recent years it has become increasingly evident that insulin-dependent diabetic patients, whether pregnant or not, run a much increased risk of having severe hypoglycaemia (SH) attacks (i.e. the patient needs the assistance of another person to relieve the attack) whenever attempts are made to introduce tight blood glucose control. Very high incidence rates of SH between 19% and 44% have been reported in diabetic pregnancy. Episodes of SH could have serious consequences; neuroglycopenia seems especially hazardous for the mother particularly during the performance of a critical task like driving a car. While hypoglycaemia has embryopathic effects in rodents, there are no data in the human to support a teratogenic effect. Insulin-induced hypoglycaemia in the last trimester of diabetic pregnancy may increase fetal body movement and decrease the fetal heart rate variability. A number of very rare conditions such as insulinoma, severe malaria, HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count), severe fulminating liver disease, and ACTH and/or growth hormone deficiency have been reported to be associated with SH. Relative hypoglycaemia--i.e. low fasting blood glucose and 'flat' glucose tolerance test--is frequently seen in normotensive pregnant women with intrauterine fetal growth retardation. This pattern of maternal carbohydrate metabolism could lead to fetal hypoglycaemia and hypoinsulinaemia and contribute to poor fetal growth.

Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes

Tight blood glucose control has been speculated to reduce late complications in insulin-dependent diabetics but results from individual studies have been inconsistent. We have done a meta-analysis of sixteen randomised trials of intensive therapy to estimate its impact on the progression of diabetic retinopathy and nephropathy and the risks of severe side-effects. In the intensive therapy group, the risk of retinopathy progression was insignificantly higher after 6-12 months of intensive control (odds ratio [OR] 2·11). After more than two years of intensive therapy the risk of retinopathy progression was lower (OR 0·49 [95% confidence interval 0·28-0·85], p=0·011). The risk of nephropathy progression was also decreased significantly (OR 0·34 [0·20-0·58], p<0·001). The incidence of severe hypoglycaemia increased by 9·1 episodes per 100 person-years (95% Cl - 1·4 to + 19·6) in the intensively treated patients. The incidence of diabetic ketoacidosis increased by 12·6 episodes per 100 person-years (95% Cl, 8·7-16·5) in the patients on continuous subcutaneous insulin infusion. Long-term intensive blood glucose control significantly reduces the risk of diabetic retinopathy and nephropathy progression but long-term continuous subcutaneous insulin infusion was associated with an increased incidence of diabetic ketoacidosis, and intensive therapy may cause more severe hypoglycaemic reactions.

7 Diabetes and adrenal disease

Disorders of the adrenal cortex and medulla can result in glucose intolerance or overt diabetes mellitus. Cushing's syndrome, characterized by excessive secretion of glucocorticoids, impairs glucose tolerance primarily by causing insulin resistance at the post-receptor level. On the other hand, phaeochromocytoma and hyperaldosteronism, via the respective actions of catecholamines and hypokalaemia on the pancreatic beta-cell, impair glucose tolerance primarily by inhibiting insulin release. The glucose intolerance associated with these adrenal disorders is usually only mild to moderate in severity. Marked hyperglycaemia, glycosuria, and polyuria are uncommon and ketosis is rare. Moreover, the late complications of diabetes mellitus are distinctly uncommon in patients with these disorders, and the prognosis for morbidity and death is usually that of the underlying disease and not that of diabetes mellitus. The impaired glucose tolerance induced by all three of these adrenal disorders usually returns to normal once the underlying aetiology has been cured. These factors must guide the clinician in treatment of these secondary forms of diabetes, and suggest that tight (near normal) blood glucose control may not be an appropriate goal in patients with these disorders. The relationship between adrenal androgens and glucose tolerance is more uncertain. Several studies in humans have demonstrated an acute decline in serum concentrations of the adrenal steroids DHEA and DHEA-sulfate in response to experimentally-induced hyperinsulinaemia, but the regulatory role of insulin on adrenal androgen metabolism in normal physiology or disease remains speculative. In several animal models DHEA appears to exert potent anti-obesity and anti-diabetogenic actions, but such effects have yet to be demonstrated in humans. Human studies of DHEA are limited, and more research needs to be conducted to determine whether the observations made in animal models will prove applicable to man.

The Future of Calcium Channel Blocker Therapy in Diabetes Mellitus

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.

Tight blood glucose control: Is it worth it?

Several investigations have assessed the relationship between glycemic control and complications in diabetes mellitus. Key evidence is reviewed that supports the beneficial effects of "tight" blood glucose control. Pertinent animal data show that good blood glucose control is associated with less retinopathy and nephropathy and fewer congenital anomalies in offspring. Short-term studies in humans show similar trends in microvascular complications and pregnancy. Similarly, peripheral neuropathy may be lessened with lower blood glucose. Although no studies have demonstrated a reduction in atherosclerotic disease with improved glycemic control, dyslipidosis frequently improves, which should reduce the risk for coronary heart and peripheral vascular disease.

Schwangerschaftsausgang unter intensivierter Insulintherapie bei manifestem Diabetes*

In 1981, the intensified insulin therapy for achievement of euglycaemia in pregnant diabetics was introduced at the University Department of Obstetrics and Gynaecology in Cologne. This study compares the results of 112 pregnancies in women with overt diabetes monitored before (1971-1980) or after (1981-1988) changing the therapeutic regimen. In the period from 1981 to 1988, the proportion of euglycaemic patients (preconceptionally 19%, before delivery 79%) was clearly higher than from 1971 to 1980 (n = 42; 7% and 9%, respectively). The tight blood glucose control resulted in a doubling of hypoglycaemic episodes during pregnancy. The proportion of preterm deliveries was reduced from 47% to 24%. The rate of caesarean sections was nearly constant (1971-1980: 38%, 1981-1988: 34%). The marked success of therapy was the decrease of perinatal mortality from 20.9% to 2.9%. The perinatal morbidity also diminished, as shown by the decreasing rates (30-90%) of foetopathy, macrosomy, respiratory distress syndrome, birth trauma, hypoglycaemia, hypocalcaemia and polycythaemia. The malformation rate, however, remained high (1971-1980 = 7%, 1981-1988 = 11%). The results demonstrate the necessity of a strict blood glucose control during pregnancy, beginning before the time of conception.

Pancreatic diabetes mellitus.

Diabetes mellitus caused by pancreatic exocrine disease is a unique clinical and metabolic form of diabetes. The diagnosis of pancreatic diabetes caused by chronic pancreatitis may be elusive because it is occasionally painless and often not accompanied by clinical malabsorption until after hyperglycemia occurs. Diabetic patients with pancreatic calcification or clinically demonstrable pancreatic exocrine dysfunction will manifest the unique aspects of pancreatic diabetes described herein. Like other forms of diabetes, the primary hormonal abnormality in pancreatic diabetes is decreased insulin secretion. Patients with this disorder are unique in that they have low glucagon levels that respond abnormally to several physiological stimuli, blunted epinephrine responses to insulin-induced hypoglycemia, and malabsorption. In addition, they often have concomitant alcohol abuse with hepatic disease and poor nutrition. These characteristics result in increased levels of circulating gluconeogenic amino acids, decreased insulin requirements, a resistance to ketosis, low cholesterol levels, an increased risk of hypoglycemia while on insulin therapy, and the clinical impression of brittle diabetes. Retinopathy occurs at a rate equal to that of insulin-dependent diabetes but may be less severe in degree. Other complications of pancreatic diabetes have been less well studied but may be expected to be seen more frequently as these patients survive longer. The characteristics of pancreatic diabetes suggest that a conservative approach be taken in regard to intensive insulin therapy and tight blood glucose control.

Brittle Diabetes in the Elderly

The term 'brittle diabetes' is now commonly used to describe patients whose lives are disrupted by major variations in metabolic control, whatever their cause. Most reports have focused on the occurrence of such problems in young people, but little attention has been paid to brittle diabetes occurring in elderly patients. We describe six such cases and comment on differences in aetiology and management when compared with younger patients. Although less rigorous objectives for tight blood glucose control as compared with younger people, and more ready acceptance of insulin administration being supervised by another person, such as a district nurse, may reduce swings in blood glucose control in the elderly, accidental mismanagement by the patient as a result of incipient or established senile dementia may be an important factor in generating instability, as was evident in three cases. In one instance, the onset of unstable diabetic control was the earliest clinical feature of mental deterioration.

Rapid Development of Proliferative Retinopathy and Autonomic Neuropathy after Tight Control of Blood Glucose in a Patient with Diabetic Ketoacidosis

Rapid Development of Proliferative Retinopathy and Autonomic Neuropathy after Tight Control of Blood Glucose in a Patient with Diabetic Ketoacidosis

Good diabetic control early in pregnancy and favorable fetal outcome : Lin C-C; River J; River P; et al. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA

This study of 74 diabetic pregnant women shows that tight maternal blood glucose control before the 32nd week of gestation significantly reduces the incidence of fetal macrosomia (11%) when compared with that of patients with fair to poor control before the 32nd week of gestation (44%, P less than .05) or with those whose good diabetic control was not achieved until after the 32nd week of gestation (34%, P less than .05). The macrosomic infant produced by a diabetic mother is associated frequently with an elevated amniotic fluid C-peptide level, which shows the evidence of intrauterine fetal hyperinsulinism. The use of tight diabetic control early in pregnancy to reduce the risk of fetal macrosomia and/or neonatal complications is of clinical importance in the management of diabetes in pregnancy.

New findings in diabetic retinopathy

Tight control of blood glucose shows promise for reducing the visual complications of juvenile diabetes, according to preliminary results of two studies presented at the recent meeting of the American Academy of Ophthalmology in Atlanta. One investigator stressed, however, that he saw no miraculous reversals of diabetic retinopathy in patients receiving continuous insulin injections from a portable pump. This is in conflict with several recent case reports of such regression. In another report also dealing with the visual complications of diabetes, ophthalmologic surgeons from the Bascom-Palmer Eye Institute in Miami described several factors that influence the outcome of vitrectomy carried out to remove vitreous opacities in retinopathic eyes. Until the results of a recently begun investigation become available, their retrospective analysis of 1,500 cases provides the best current guidelines for determining which patients have the greatest chance of benefiting from this procedure. Glucose Control.— There long has been a dispute