Prehospital treatment of severe hypoglycaemia: a comparison of intramuscular glucagon and intravenous glucose.

INTRODUCTION: By introducing an intensified insulin treatment regime to patients with insulin-dependent diabetes mellitus (IDDM), the frequency of long-term complications that the patient will experience has been shown to decrease. The price is an increase in the frequency of severe and mild hypoglycaemic events. Therefore, constant monitoring of these patients is necessary. HYPOTHESIS: This study compares the time until full recovery of IDDM patients with severe hypoglycaemia after treatment with either intravenous glucose or intramuscular glucagon. METHODS: 14 patients with IDDM with severe hypoglycaemia requiring treatment by the medical staff was randomised to treatment either with 50 ml of 50% glucose intravenously or intramuscular 1 mg glucagon. The time to recovery was recorded. Plasma glucose was measured at fixed intervals to achieve a glycaemia profile. Demographic data were acquired through patient interviews following recovery. RESULTS: Recovery time between the two groups was significantly different statistically. Recovery time ranged for 1 to 3 minutes for those receiving glucose intravenously and 8 to 21 minutes for those receiving intramuscular glucagon. Characteristic glycaemia profiles were identified and differences were present between the two groups with a greater fluctuating pattern for the glucose group compared to the steadily increasing pattern seen after glucagon treatment. Alcohol was believed to be involved in 8 out of the 14 cases, and thereby, is the major confounding factor in this study. CONCLUSION: Intramuscularly administered glucagon is a safe and reliable alternative to intravenous glucose infusion. The fluctuating glycemia pattern seen after glucose treatment indicates a low risk for secondary hypoglycaemia. However, further studies are necessary to support this assertion.     

Comparison of intramuscular glucagon and intravenous dextrose in the treatment of hypoglycaemic coma in an accident and emergency department.

Hypoglycaemia remains a serious and much feared complication of insulin therapy. In this study, patients attending an accident and emergency department in hypoglycaemic coma were randomized to treatment with either intravenous dextrose (25g) or intramuscular glucagon (1mg), administered into the right thigh. Restoration of normal conscious level was slower after glucagon than dextrose (9.0 vs 3.0 min, P less than 0.01), although the average duration of hypoglycaemic coma was 120 min. Two patients in the glucagon-treated group, who failed to show satisfactory recovery after 15 min, required additional treatment with intravenous dextrose. On questioning following recovery, all except two patients reported loss of awareness of the onset of hypoglycaemia Intramuscular glucagon is valuable in the treatment of severe hypoglycaemia outwith hospital and, although the slightly slower and less predictable recovery may appear to make it a less attractive option than intravenous dextrose in the accident and emergency department, this must be balanced against the advantages of ease of administration and a lower incidence of serious adverse effects.     

A comparison of glycaemic variability in CSII vs. MDI treated type 1 diabetic patients using CGMS

Objective: To evaluate and compare glucose variability, hypoglycaemic events and daily glycaemic control in well‐controlled (HbA1c ≤ 7%), type 1 diabetic patients treated with either continuous subcutaneous insulin infusion (CSII) using lispro or multiple daily insulin injection (MDI) using glargine once daily and lispro with meals. Research design and methods: A total of 16 patients with type 1 diabetes receiving treatment with either CSII (eight patients) or MDI (eight patients), all with HbA1c levels < 7%, wore a continuous glucose monitoring system sensor for 3 days to compare the number, duration, timing and severity of hyperglycaemic and hypoglycaemic episodes. Results: There were several more episodes of hyperglycaemic [blood glucose (BG) ≥ 180 mg/dl] and hypoglycaemic (BG ≤ 60 mg/dl) excursions observed in patients treated with CSII than MDI. Glycaemic exposure over 150 mg/dl was similar between the two groups. Maintenance of near‐euglycaemia as determined by the average amount of time spent within the glucose range of 80–140 mg/dl was marginally significantly better for the MDI than for the CSII group. Although the CSII group had significantly more hypoglycaemic episodes below 60 mg/dl, the average duration of hypoglycaemia was not significantly different for the two groups. Similar percentages of nocturnal hypoglycaemia were seen. There were no reported major adverse events throughout the duration of the study. Conclusion: Well‐controlled type 1 diabetic patients treated with MDI had fewer hyperglycaemic and hypoglycaemic excursions than patients treated with CSII.     

No differential effects of porcine and human insulin on muscle sympathetic nerve activity during euglycaemia or hypoglycaemia

Summary. On the basis of some clinical studies in diabetic patients, and experimental studies in normal humans, it has been suggested that hypoglycaemic autonomic responses are augmented with porcine (PI) compared to human insulin (HI). A difference in sensory processing has been reported following insulin-induced hypoglycaemia with PI compared to HI, and has been interpreted as different insulin effects on the central nervous system. In a double blind crossover comparison of HI and PI in nine healthy subjects, microneurographic recordings of muscle sympathetic nerve activity (MSNA) were performed, as well as measurements of cardiovascular and hormonal responses during a low dose hyperinsulinaemic euglycaemic glucose clamp (plasma insulin 60.1 ±1.9 mU ml^-1 (mean ± SEM)), followed by a period of insulin-induced hypoglycaemia. Plasma insulin and glucose were identical in the two sessions. Plasma glucose nadir during hypoglycaemia was 2.4 ± 0.2 mmol 1^-1 for HI and 2.5 ±0.1 mmol l^-1 for PI. During euglycaemia, MSNA increased from 24 ± 2 to 34 ± 3 and 23 ± 2 to 30 ± 2 burst/min (P:NS) for HI and PI, respectively, and during hypoglycaemia to 49 ± 4 and 45 ± 2 bursts min^-1 (P:NS), respectively. The maximal hypoglycaemic increments of MSNA were not different (HI 15 ± 4; PI 15 ± 2 bursts min^-1 (P: NS)) Responses of plasma noradrenaline and haemodynamic parameters did not differ either. This study does not indicate differing sympathetic responses to PI and HI in healthy humans. Evidence for a modulating effect of insulin on central sympathetic outflow was not found.     

Pulmonary hypertension,heart failure and neutropenia due to diazoxide therapy

Primary persistent hyperinsulinaemic hypoglycaemia is characterised by clinical symptoms that occur when blood glucose levels drop below the normal range. Diazoxide treatment remains the mainstay of medical therapy. Tolerance of diazoxide is usually excellent, but several side effects of this drug have been described. We present a 4-month-old girl who developed pulmonary hypertension, heart failure and neutropenia during diazoxide therapy. Diazoxide toxicity was suspected and the drug was withdrawn on day 13. During the next 3 days, respiratory and haemodynamic status dramatically improved and she was weaned from mechanical ventilation. Control white blood cell count was 8800 cells/mm(3) and a new echocardiography showed modreduction of pulmonary artificial pressure to 20 mmHg and resolution of atrial and ventricular enlargement. Paediatric physicians should be in mind of pulmonary hypertension, heart failure and neutropenia developing during diazoxide therapy.     

Effects of insulin per se on neuroendocrine and metabolic counter-regulatory responses to hypoglycaemia

We examined and compared findings from studies aimed at detecting and quantifying an effect of insulin per se on counter-regulatory responses to hypoglycaemia. The experimental protocols used in many of these studies were very different with regard to study design and patient population, resulting at times in inconsistencies and discrepancies. Taken together, the results from this extensive body of work clearly indicate that, at similar levels of hypoglycaemia, greater hyperinsulinaemia results in enhanced counter-regulatory responses. This enhancement includes higher circulating levels of counter-regulatory hormones (adrenaline, noradrenaline, cortisol and growth hormone, but not glucagon), more intense activation of hypoglycaemic symptoms (both neural-sympathetic and adrenal-sympathetic), and greater deterioration of neuropsychological skills. The insulin-induced enhancement of counter-regulatory responses is not influenced by gender, is present in several animal species, and applies to healthy subjects as well as to patients with Type I diabetes. The underlying mechanisms remain speculative, and possibly include a direct neuromodulatory effect and/or suppression of glucose utilization in various areas of the brain, which either independently or in a hierarchical fashion trigger the sequence of downstream counter-regulatory events.     

A hyperinsulinaemic, sequentially eu- and hypoglycaemic clamp test to characterize autonomous insulin secretion in patients with insulinoma

To better characterize autonomous insulin secretory behaviour in insulinoma patients and to establish diagnostic criteria with high accuracy, hyperinsulinaemic, sequentially eu- and hypoglycaemic clamp tests were performed in insulinoma patients and control subjects. Ten patients with insulinoma (benign in nine, histologically proven in nine) and 10 patients with suspected episodes of hypoglycaemia, in whom thorough clinical evaluation excluded an insulinoma, were examined. Five insulinoma patients were restudied after successful extirpation of the tumour. Suppression of C-peptide during low-dose [2 pmol kg^–1 min^–1 (20 mU kg^–1h^–1) for 90 min, plasma insulin approximately 120 pmol L^–1 (20 mU L^–1)] and high-dose [8 pmol kg^–1 h^–1 (80 mU kg^–1 h^–1) for 90 min, plasma insulin approximately 450 pmol L^–1 (75 mU L^–1)] insulin infusion under euglycaemic conditions [plasma glucose 4.4–5.0 mmol L^–1 (80–90 mg dL^–1)]) and during high-dose insulin infusion under hypoglycaemic conditions [glucose 2–2.2 mmol L^–1 (40–45 mg dL^–1)] was evaluated by radioimmunoassay (RIA). Euglycaemic hyperinsulinaemia suppressed C-peptide in control subjects (P < 0.0001), whereas in insulinoma patients apparently irregular changes in C-peptide concentrations (with spontaneous or paradoxical increments, P = 0.0006 vs. controls) were observed. The combination of hyperinsulinaemia and controlled hypoglycaemia led to a nearly complete suppression of C-peptide in normal subjects (from basal, 0.76 ± 0.08–0.06 ± 0.01 nmol L^–1; maximum observed value 0.10 nmol L^–1), which was more pronounced than at the point of discontinuation of prolonged fasting (> 48 h; 0.26 ± 0.16 nmol L^–1; P = 0.005). In insulinoma patients, C-peptide remained elevated under all conditions (P = 0.51 vs. prolonged fasting). All these findings were reversible after successful surgical removal of the insulinoma. Insulinoma patients could be identified as abnormal by (a) non-suppression of C-peptide even under hyperinsulinaemic/hypoglycaemic conditions (10 out of 10 patients) and (b) irregular increments in C-peptide under conditions that led to at least partial suppression in all normal subjects (9 out of 10 patients) and/or by an apparent shift to the left of insulin secretion relative to glucose concentrations (7 out of 10 patients). Controlled exposure to hyperinsulinaemic/hypoglycaemic conditions can help to characterize autonomous secretion in insulinoma patients and may be used as a diagnostic procedure when conventional methods yield equivocal results.     

Targeting glucagon receptor signalling in treating metabolic syndrome and renal injury in Type 2 diabetes: theory versus promise

Pancreatic bi-hormones insulin and glucagon are the Yin and Yang in the regulation of glucose metabolism and homoeostasis. Insulin is synthesized primarily by pancreatic beta-cells and is released in response to an increase in blood glucose levels (hyperglycaemia). By contrast, glucagon is synthesized by pancreatic alpha-cells and is released in response to a decrease in blood glucose (hypoglycaemia). The principal role of glucagon is to counter the actions of insulin on blood glucose homoeostasis, but it also has diverse non-hyperglycaemic actions. Although Type 1 diabetes is caused by insulin deficiency (insulin-dependent) and can be corrected by insulin replacement, Type 2 diabetes is a multifactorial disease and its treatment is not dependent on insulin therapy alone. Type 2 diabetes in humans is characterized by increased insulin resistance, increased fasting blood glucose, impaired glucose tolerance and the development of glomerular hyperfiltration and microalbuminuria, ultimately leading to diabetic nephropathy and end-stage renal disease. Clinical studies have suggested that an inappropriate increase in hyperglycaemic glucagon (hyperglucagonaemia) over hypoglycaemic insulin (not insulin deficiency until advanced stages) plays an important role in the pathogenesis of Type 2 diabetes. However, for decades, research efforts and resources have been devoted overwhelmingly to studying the role of insulin and insulin-replacement therapy. By contrast, the implication of glucagon and its receptor signalling in the development of Type 2 diabetic metabolic syndromes and end-organ injury has received little attention. The aim of this review is to examine the evidence as to whether glucagon and its receptor signalling play any role(s) in the pathogenesis of Type 2 diabetic renal injury, and to explore whether targeting glucagon receptor signalling remains only a theoretical antidiabetic strategy in Type 2 diabetes or may realize its promise in the future.     

Hypoglycaemia--diagnosis and therapy in emergencies

Hypoglycaemia defined as blood sugar below 2.5 mmol/L, is always an important medical emergency. The primary therapy is simple and consists of iv glucose. The occurrence of hypoglycaemia is directly connected to fuel balance, determined by the availability of glucose, free fatty acids and ketone bodies. An intact fuel balance and maintenance of normal blood sugar concentration is dependent upon: (1) an adequate caloric and qualitative dietary intake; (2) afunctionally intact hepatic glucogenolytic and gluconeogenic enzyme system; (3) an adequate supply of endogenous gluconeogenic substrates (lactate, amino acids and glycerol) (4) an adequate energy supply provided by the beta-oxidation of fatty acids to synthesize glucose and ketone bodies and (5) a normal endocrine system (insulin, glucagon, catecholamines and growth hormone) for integrating and modulating these processes. Disturbances in each of these factors may lead to hypoglycaemia. Glucose, like oxygen, is of essential and fundamental importance for the brain metabolism. The major contribution of the brain to the basal metabolic rate (70% in neonates versus 20% in adults) is an important factor contributing to the frequency and severity of a hypoglycaemic syndrome in the paediatric age. If hypoglycaemia is suspected, blood should be obtained prior to treatment for serum glucose determination and an extra tube (5 ml) serum should be obtained and refrigerated for further investigations. The first voided urine has to be tested for ketones using a dipstick and also refrigerated for further investigations. Basic laboratory investigations, anamnestic informations and clinical findings allow rapid tentative diagnosis and determine the specialized investigations out of the refrigerated material. A rapid definitive diagnosis is important for the specific treatment and to avoid recurrent and prolonged hypoglycaemia.     

On the diabetogenic effect of growth hormone in man: effects of growth hormone on glucagon and insulin secretion

Abstract. The effects of human growth hormone (GH) on glucose homeostasis and the secretion of insulin and glucagon was investigated in eighteen healthy subjects. GH (40 μg/kg) was given as a 30 min i.v. infusion and was followed immediately, or after 60 min, by either a glucose infusion, or an i.v. L-arginine infusion or i.v. insulin (005 IU/kg).
An insulin-like effect of GH was seen about 15 min after the start of the GH infusion, and became a diabetogenic action 90 min later. Basal and glucose stimulated insulin secretion were suppressed 60 min after the start of the GH infusion, while insulin response to i.v. L-arginine, on the whole, was uninfluenced. Basal glucagon as well as glucagon response to arginine or hypoglycaemia were uninfluenced by GH. GH did not alter the degree of hypoglycaemia reached after i.v. insulin, whereas the rapidity of blood glucose fall was significantly decreased. The restitution of blood glucose after its nadir was not modified by the hormone.
These results demonstrate that the diabetogenic action of GH is not mediated by GH effects on glucagon secretion, and that GH is of little importance in the acute counter-regulation of insulin-induced hypoglycaemia.     

Physiological disturbances in hypoglycaemia: effect on subjective awareness.

Deficiencies in the release of glucagon and adrenaline during hypoglycaemia in diabetic patients are associated with a high frequency of severe hypoglycaemic episodes. These have been attributed to a resulting inability to increase hepatic glucose output acutely. A more important consequence may be reduced awareness of impending hypoglycaemia. Such hypoglycaemia unawareness is related to, but not entirely explained by, diminished sympathetic activity, perhaps due to failure to activate the sympathoadrenal system until a lower blood glucose level is achieved. The patient's subsequent failure to act appropriately would then be due to impaired cerebral function preventing the perception of sympathoadrenal activation during the more severe hypoglycaemia. Unawareness of moderate hypoglycaemia is common in diabetic patients. Autonomic neuropathy probably accounts for only a few cases of hypoglycaemia unawareness and other factors which are potentially important include duration of diabetes, glycaemic control, insulin species, and the degree and frequency of hypoglycaemia. Further research is required to discover both the pathophysiological mechanisms of, and the treatment needed to reverse or prevent, the abnormality.     

Insulin glargine (Lantus)

Insulin glargine (Lantus) is a long-acting, human insulin analogue that has been specifically designed to overcome the deficiencies of traditionally available 'intermediate-acting' insulins that are currently used for basal insulin supplementation. In contrast to NPH insulin, subcutaneous insulin glargine injected once daily provides a relatively constant basal level of circulating insulin with no pronounced peak. In patients with type 1 and type 2 diabetes, once-daily insulin glargine achieves equivalent glycaemic control to NPH insulin given once or twice daily In patients with type 1 diabetes, it is associated with significantly lower fasting blood glucose (FBG) levels, especially in those patients previously on twice-daily NPH insulin. Insulin glargine is well tolerated and elicits less hypoglycaemia, especially nocturnal episodes, than NPH insulin, with similar levels of glycaemic control. This benefit is seen in patients with both type 1 and type 2 diabetes, in particular those previously on a once-daily NPH insulin regimen. Patients with type 1 and type 2 diabetes have also reported higher levels of treatment satisfaction when treated with insulin glargine. Insulin glargine provides the opportunity to achieve target blood glucose levels more effectively and safely compared with NPH insulin, due to the reduced risk of hypoglycaemia, especially nocturnal hypoglycaemia. Insulin treatment needs to be individualised, with the dose of insulin glargine adjusted according to the blood glucose level as part of an aggressive regimen in an attempt to achieve near normoglycaemia without incurring episodes of hypoglycaemia. Insulin glargine should be used in combination with short-acting insulin analogues in patients with type 1 diabetes. In patients where oral hypoglycaemic agents are failing, insulin glargine can be added. The early introduction of insulin in patients with type 2 diabetes is to be encouraged.     

Islet cell function: alpha and beta cells--partners towards normoglycaemia

Under normal conditions, insulin and glucagon are counter-regulatory hormones whose balanced action exhibits a relationship that ensures normoglycaemia. Elevated glucose levels following a meal stimulate pancreatic islet beta cells to secrete insulin and islet alpha cells to downregulate production of glucagon. With declining glucose and insulin levels, alpha-cell production of glucagon is increased to stimulate hepatic glucose production, preventing fasting hypoglycaemia. In type 2 diabetes mellitus (T2DM), beta-cell insulin response to glucose is blunted, including absence of early acute response, and alpha-cell response to glucose is impaired, resulting in absolute or relative hyperglucagonaemia and inappropriate hepatic glucose output that contributes to fasting hyperglycaemia. These changes are associated with structural and functional changes in pancreatic islets, including reduced beta-cell mass and reduced beta-cell:alpha-cell ratio. The role of the incretin hormone glucagon-like peptide-1 (GLP-1) in regulating glucose-dependent beta-cell insulin production and glucose-dependent alpha-cell glucagon production has been used to develop GLP-1-based therapies. These therapies may reduce the imbalances among insulin and glucagon that characterise T2DM, resulting in improved glycaemic control.     

Continuous blood glucose monitoring: detection and prevention of hypoglycaemia

For patients with diabetes the best defence against the consequences of either hypoglycaemia or hyperglycaemia is to be able to recognise it and treat it promptly. In normal activity patients have problems in their diabetes management despite adequate knowledge and therapies. Glucose sensors have been developed that can be inserted subcutaneously in order to continuously monitor glucose concentrations over several days. Studies have been conducted with continuous glucose monitoring of patients with diabetes that reveal previously unrecognised periods of hypoglycaemia, ranging from a few minutes to several hours. Continuous monitoring during the nocturnal period can reveal hypoglycaemic and hyperglycaemic episodes and the insulin usage can subsequently be adjusted to decrease the incidence, which may lead to reduction in the risk of long-term complications. Preliminary studies have already shown that better management can be obtained, with reductions in HbA1c levels, when 24-h profiles of glucose concentrations are obtained. Our ongoing study of patients with type 1 diabetes assessing continuous glucose monitoring have shown that glucose concentrations are only within a target range of 4-10 mmol/l for about 35 per cent of the time. Such measurements are leading to better individualisation of diabetes management. While the present generation of glucose monitors only provide retrospective profiles, newer sensors are being developed that can detect real-time changes. These may form the basis of an alert to hypoglycaemic levels or ultimately be connected directly to continuous insulin infusion, particularly with rapid-acting insulin analogues, to maintain glucose within normal physiological limits.     

Increased symptoms of hypoglycaemia in the standing position in insulin-dependent diabetes mellitus.

1. To test the hypothesis that patients with insulin-dependent diabetes mellitus perceive the symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position, we assessed symptoms of hypoglycaemia, as well as heart rate and plasma noradrenaline and adrenaline concentrations, in both positions during hyperinsulinaemic glucose clamps on three occasions in seven patients. 2. Plasma glucose concentrations were clamped at 5.0 mmol/l (90 mg/dl) and 5.0 mmol/l on one occasion, at 5.0 mmol/l and 3.9 mmol/l (70 mg/dl) on another occasion, and at 5.0 mmol/l and 2.8 mmol/l (50 mg/dl) on yet another occasion. 3. During euglycaemia there was no effect of position on the symptom panels used to assess the symptomatic response to hypoglycaemia. However, at the plasma glucose concentration of 2.8 mmol/l, total (P less than 0.003) and neurogenic (P less than 0.005), but not neuroglycopenic, hypoglycaemic symptom scores were higher with the patients in the standing than in the lying position. Increments in total hypoglycaemic symptom scores, over those during the corresponding euglycaemic phase, were 5 +/- 2 in the lying position and 11 +/- 2 in the standing position (means +/- SEM, P less than 0.01). 4. Thus patients with insulin-dependent diabetes mellitus perceive symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position because of enhanced neurogenic symptoms.     

Optimal blood glucose control in severely burned patients: a long way to go,but one step closer

Over the past years there has been a significant decrease in mortality and morbidity in patients suffering from severe burns due to improved burn wound management and approaches in critical care. Survival is no longer the exception, but unfortunately death still occurs. One of the key elements concerning state-of-the-art burn care is blood glucose control and insulin therapy; it is well known that burn-induced hyperglycaemia is associated with adverse clinical outcomes. However, controversy for insulin therapy and tight glycaemic control in critically ill and burn patients exists. The increased incidence of hypoglycaemia is the dominant argument against this treatment, because hypoglycaemia is also associated with an increased risk for death in critically ill patients. Taking all current data together, insulin therapy appears both a friend and a foe in the treatment of ICU patients. In order to overcome the limits of tight glycaemic control resulting from hypoglycaemic episodes, current efforts have been directed towards the development of protocols allowing for implementation of clinically feasible and safe guidelines. Among the strategies addressing this problem are closed loop techniques, which are supported by studies demonstrating their capability of exerting tight glycaemic control without the risk of developing hypoglycaemic episodes. Although closed loop techniques have become readily available, we require further evidence to ensure their safety in various ICU environments, notably in ICUs dealing with burn patients. Nonetheless, it is important to emphasise that glycaemic control and adequate insulin therapy are crucial factors for the final outcome (survival) and require our attention.     

Safety and efficacy of insulin detemir in clinical practice: 14-week follow-up data from type 1 and type 2 diabetes patients in the PREDICTIVE European cohort

PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, open-label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. A total of 20,531 patients with type 1 or 2 diabetes from 11 countries were prescribed insulin detemir and followed up after a mean of 14.4 weeks. The primary endpoint was incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary endpoints were: haemoglobin A(1c) (HbA(1c)), mean self-monitored fasting glucose, within-patient fasting glucose variability and body weight change. Two hundred and fourteen patients (1%) reported SADRs, including major hypoglycaemia. The incidence of major hypoglycaemic episodes was reduced from 3.0/patient-year at baseline to 0.7/patient-year at follow-up in type 1 patients (p < 0.0001), and from 0.8 to 0.1/patient-year in type 2 patients (p < 0.0001). Insulin detemir improved glycaemic control in type 1 and type 2 patients, with reductions in mean HbA(1c) (0.5% and 0.9%, respectively, p < 0.0001 for both), fasting glucose (1.7 and 2.6 mmol/l, p < 0.0001 for both) and within-patient fasting glucose variability (0.7 and 0.5 mmol/l, p < 0.0001 for both). There was a small decrease in mean body weight in both type 1 and 2 patients (-0.1 kg, p < 0.01 and -0.4 kg, p < 0.0001 respectively). Insulin detemir was used once- or twice-daily in 49% and 50% of type 1 patients, and 77% and 23% of type 2 diabetes patients, respectively. The 14-week observations from PREDICTIVE support clinical trial data showing that insulin detemir improves glycaemic control, with a lowered risk of hypoglycaemia and no weight gain.     

Addition of exenatide twice daily to basal insulin for the treatment of type 2 diabetes: clinical studies and practical approaches to therapy

Background: Type 2 diabetes is a progressive disease that requires stepwise additions of non‐insulin and insulin therapies to meet recommended glycaemic goals. The final stage of intensification may require prandial insulin, adding complexity and increased risks of hypoglycaemia and weight gain. Aims: This review assesses the benefits and risks of adding exenatide twice daily, a glucagon‐like peptide 1 receptor agonist, in patients with type 2 diabetes who are currently treated with basal insulin, but have failed to reach their glycaemic goals. Methods and Results: Based on data from published studies, exenatide has a number of actions that complement basal insulin therapy. Exenatide has been shown to increase glucose‐dependent insulin production, suppress abnormal plasma glucagon production, slow gastric emptying, enhance liver uptake of glucose and promote satiety. A recently published randomised clinical trial reported that the addition of exenatide twice daily to titrated basal insulin provided greater glycaemic control than titrated basal insulin alone, and did so without an increase in hypoglycaemic events and with modest weight loss. Exenatide use was associated with gastrointestinal side effects. The recent randomised trial confirmed and extended data from a number of prior observational studies that demonstrated the efficacy and safety of insulin/exenatide combination therapy. Practical considerations for adding exenatide twice daily to ongoing basal insulin are discussed.     

A comparison of insulin doses for treatment of hyperkalaemia in intensive care unit patients with renal insufficiency

BackgroundHyperkalaemia is a complication in patients with chronic kidney disease or acute kidney injury and occurs frequently in the intensive care unit. One treatment approach includes intravenous (IV) insulin to shift potassium intracellularly.ObjectivesThe primary outcome was hypoglycaemia (blood glucose <70 mg/dL) after insulin administration. Secondary outcomes included change in serum potassium levels and incidence of severe hypoglycaemia.MethodsThis was a single-centre, retrospective study evaluating critically ill adult patients with chronic kidney disease stage III–V, end-stage renal disease, or acute kidney injury who received IV insulin for treatment of hyperkalaemia from March 2008 to September 2018. Patients were divided into two insulin-dosing regimen groups: 5 units or 10 units.ResultsOf the 174 patients included, hypoglycaemia after insulin administration occurred in eight of 87 patients (9.2%) in the 5-unit group and 17 of 87 patients (19.5%) in the 10-unit group (p = 0.052). There was no difference in rates of severe hypoglycaemia or change in serum potassium levels.ConclusionsIn critically ill patients requiring treatment for hyperkalaemia, a lower dose of IV insulin does not result in lower statistically significant rates of hypoglycaemia. However, lower insulin doses provide a similar potassium-lowering effect and cause a meaningful decrease in hypoglycaemic episodes. Intensive care unit providers may consider 5 units of IV insulin over 10 units although further larger controlled studies are needed.     

Hypoglycaemia and counterregulatory hormone responses in severe falciparum malaria: treatment with Sandostatin

The mechanism and response to treatment of severe life–threateninghypoglycaemia (plasma glucose 1.15±0.73 mM/I [±SD])was studied in eight Thai patients with falciparum malaria.Plasma insulin concentrations were inappropriately high (range1.0–21.8 mU/I), lactic acidosis was common (arterial bloodlactic acid concentration 1.44—17.8 mM/I), but the glucosecounterregulatory response, indicated by plasma cortisol, growthhormone, catecholamines and glucagon concentrations, was intactHyperinsulinaemia was successfully treated in five patientsby a continuous intravenous infusion of the long–actingsomatostatin analogue Sandostatin (SMS 201—995), 50 µg/h.In volunteer studies a single intramuscular injection of Sandostatin(100 µg) suppressed quinine–induced hyperinsulinaemiawithin 15 min; this effect was maintained for 6 h. These resultssuggest that Sandostatin may be a safe and effective way ofcorrecting the hyperinsulinaemic hypoglycaemia complicatingquinine treatment of falciparum malaria. This treatment couldbe particularly useful in fluid–overloaded patients withrecurrent hypoglycaemia despite dextrose infusions.