Management of critically ill patients with type 2 diabetes:The need for personalised therapy

Critical illness in patients with pre-existing diabetes frequently causes deterioration in glycaemic control.Despite the prevalence of diabetes in patients admitted to hospital and intensive care units,the ideal management of hyperglycaemia in these groups is uncertain.There are data that suggest that acute hyperglycaemia in critically ill patients without diabetes is associated with increased mortality and morbidity.Exogenous insulin to keep blood glucose concentrations 10 mmol/L is accepted as standard of care in this group.However,preliminary data have recently been reported that suggest that chronic hyperglycaemia may result in conditioning,which protects these patients against damage mediated by acute hyperglycaemia.Furthermore,acute glucose-lowering to 10 mmol/L in patients with diabetes with inadequate glycaemic control prior to their critical illness appears to have the capacity to cause harm.This review focuses on glycaemic control in critically ill patients with type 2 diabetes,the potential for harm from glucose-lowering and the rationale for personalised therapy.     

Whey protein: The “whey” forward for treatment of type 2 diabetes?

A cost-effective nutritional approach to improve postprandial glycaemia is attractive considering the rising burden of diabetes throughout the world. Whey protein, a by-product of the cheese-making process, can be used to manipulate gut function in order to slow gastric emptying and stimulate incretin hormone secretion, thereby attenuating postprandial glycaemic excursions. The function of the gastrointestinal tract plays a pivotal role in glucose homeostasis, particularly during the postprandial period, and this review will discuss the mechanisms by which whey protein slows gastric emptying and stimulates release of gut peptides, including the incretins. Whey protein is also a rich source of amino acids, and these can directly stimulate beta cells to secrete insulin, which contributes to the reduction in postprandial glycaemia. Appetite is suppressed with consumption of whey, due to its effects on the gut-brain axis and the hypothalamus. These properties of whey protein suggest its potential in the management of type 2 diabetes. However, the optimal dose and timing of whey protein ingestion are yet to be defined, and studies are required to examine the long-term benefits of whey consumption for overall glycaemic control.     

Phimosis as a presenting feature of diabetes

OBJECTIVE

To determine the prevalence of diabetes in men presenting with phimosis, and to establish the incidence of undiagnosed diabetes in men presenting with acquired or life‐long phimosis.

PATIENTS AND METHODS

We prospectively collected data on 100 men (mean age 38.5 years, range 17–82) who presented to our department with phimosis during 2006. Urinary glucose levels and random serum glucose levels were analysed, and if abnormal, the patient had further diagnostic tests for diabetes.

RESULTS

In all, 31 men presented with a life‐long history of phimosis and 69 with a history of acquired phimosis. There was no history of diabetes and no abnormal serum glucose levels in those with life‐long phimosis. Eighteen of 69 (26%) of those with acquired phimosis had a history of type 2 diabetes. Type 2 diabetes was newly diagnosed in four of 50 (8%) men presenting with acquired phimosis and no history of a glycaemic disorder. A further two (4%) were diagnosed with impaired fasting glycaemia and impaired glucose tolerance. Urine analysis was positive for glucose in all new diagnoses of glycaemic disorders, except in one man.

CONCLUSION

Diabetes can be associated with acquired phimosis in almost a third of cases, and 12% of men presenting with acquired phimosis and no history of diabetes were diagnosed with a disorder of glycaemic control. Therefore it is important that serum glucose levels are analysed when assessing men with acquired phimosis.     

Assessment of markers of glycaemic control in diabetic patients with chronic kidney disease using continuous glucose monitoring

Aim: Due to altered red blood cell survival and erythropoietin therapy glycated haemoglobin (HbA1c) may not accurately reflect long‐term glycaemic control in patients with diabetes and chronic kidney disease (CKD). Glycated albumin (GA) and fructosamine are alternative markers of glycaemia. The aim of this study was to investigate the accuracy of HbA1c, GA and fructosamine as indicators of glycaemic control using continuous glucose monitoring. Methods: HbA1c, GA and fructosamine concentrations were measured in 25 subjects with diabetic nephropathy (CKD stages 4 and 5 (estimated glomerular filtration rate <30 mL/min per 1.73 m²)) matched with 25 subjects with diabetes and no evidence of nephropathy. Simultaneous real‐time glucose concentrations were monitored by continuous glucose monitoring over 48 h. Results: GA correlated significantly to mean glucose concentrations in patients with and without CKD (r = 0.54 vs 0.49, P < 0.05). A similar relationship was observed with fructosamine relative to glucose. A poor correlation between HbA1c and glucose was observed with CKD (r = 0.38, P = ns) but was significant in the non‐CKD group (r = 0.66, P < 0.001). The GA/HbA1c ratio was significantly higher in diabetic patients with CKD compared with controls (2.5 ± 0.4 vs 2.2 ± 0.4, P < 0.05). HbA1c values were significantly lower in CKD patients, relative to non‐CKD patients at comparable mean glucose concentrations. Conclusion: HbA1c significantly underestimates glycaemic control in patients with diabetes and CKD stages 4 and 5. In severe CKD, GA more accurately reflects glycaemic control compared with fructosamine and HbA1c and should be the preferred marker of glycaemic control.     

Current and future impact of clinical gastrointestinal research on patient care in diabetes mellitus

The worldwide rise in the prevalence of obesity supports the need for an increased interaction between ongoing clinical research in the allied fields of gastrointestinal medicine/surgery and diabetes mellitus. There have been a number of clinically-relevant advances in diabetes, obesity, and metabolic syndrome emanating from gastroenterological research. Gastric emptying is a significant factor in the development of upper gastrointestinal symptoms. However, it is not the only mechanism whereby such symptoms occur in patients with diabetes. Disorders of intrinsic pacing are involved in the control of stomach motility in patients with gastroparesis; on the other hand, there is limited impact of glycemic control on gastric emptying in patients with established diabetic gastroparesis. Upper gastrointestinal functions related to emptying and satiations are significantly associated with weight gain in obesity. Medications used in the treatment of diabetes or metabolic syndrome, particularly those related to pancreatic hormones and incretins affect upper gastrointestinal tract function and reduce hyperglycemia and facilitate weight loss. The degree of gastric emptying delay is significantly correlated with the weight loss in response to liraglutide, a glucagonlike peptide-1 analog. Network meta-analysis shows that liraglutide is one of the two most efficacious medical treatments of obesity, the other being the combination treatment phentermine-topiramate. Interventional therapies for the joint management of obesity and diabetes mellitus include newer endoscopic procedures, which require long-term follow-up and bariatric surgical procedure for which long-term follow up shows advantages for individuals with diabetes. Newer bariatric procedures are presently undergoing clinical evaluation. On the horizon, combination therapies, in part directed at gastrointestinal functions, appear promising for these indications. Ongoing and future gastroenterological research when translated to care of individuals with diabetes mellitus should provide additional options to improve their clinical outcomes.     

Perioperative management of diabetes and corticosteroid supplementation

Diabetes is one of the most common endocrinopathies with increasing global prevalence. More patients with severe diabetes require elective and emergency surgery. Diabetes is also associated with increased postoperative morbidity and mortality. It is essential that good glycaemic control is maintained to avoid complications related to both hyperglycaemia and hypoglycaemia. Historically, the means of achieving this has been variable, but there is now a large volume of data underlying recommendations for good glycaemic control. The Joint British Diabetes Societies for Inpatient Care Group (JBDS-IP) have provided updated guidance on the management of adults with diabetes undergoing surgery and elective procedures. The management of glycaemia in the intensive care setting is beyond the remit of this article. Ideally, hospitals should have a diabetes consultant lead for this service and inpatient diabetes nurse teams to help facilitate optimal management. Corticosteroids are amongst the most common medications prescribed for a variety of medical conditions. Corticosteroids can result in suppression of hypothalamic–pituitary–adrenal (HPA) axis and patients on corticosteroids are unable to mount an effective stress response to surgery. This article aims to give guidance and provide protocols for the effective perioperative management of diabetes and glucocorticoid replacement. Data on the need for supra-physiological corticosteroid doses are based on two small randomized controlled trials and other observational studies; highlighting the need for further research in this area.     

Perioperative management of diabetes and corticosteroid supplementation

Diabetes is one of the most common endocrinopathies with increasing prevalence worldwide. More patients with severe diabetes require elective and emergency surgery. Diabetes is also associated with increased postoperative morbidity and mortality. It is essential that good glycaemic control is maintained to avoid complications related to both hyperglycaemia and hypoglycaemia. Historically, the means of achieving this has been variable, but there is now a large volume of data underlying recommendations for good glycaemic control. The Joint British Diabetes Societies for Inpatient Care Group, alongside other societies including Diabetes UK and the British Association of Day Surgery have provided updated guidance on the management of adults with diabetes undergoing surgery and elective procedures. The management of glycaemia in the intensive care setting is beyond the remit of this article. Ideally, all hospitals should have a diabetes consultant lead for this service and inpatient diabetes nurse teams to help facilitate optimal management. Corticosteroids are amongst the most common medications prescribed for variety of medical conditions. This can result in suppression of hypothalamic–pituitary–adrenal (HPA) axis and patients on corticosteroids are unable to mount an effective stress response to surgery. This article aims to give guidance and provide protocols for the effective perioperative management of diabetes and glucocorticoid replacement. Data on the need for supra-physiological corticosteroid doses are based on two small randomized controlled trials and other observational studies; highlighting the need for further research in this area.     

Diabetes mellitus Typ 2

Type 2 diabetes and impaired glucose tolerance are an increasing burden not only for affected patients, but also for the whole health care system. The pathophysiology of diabetes and its late complications are far from being understood with hyperglycaemia being only the last sign of a long lasting and complex metabolic dysfunction. One major problem in finding therapeutic targets is the fact that the cellular disorders responsible for the development of diabetes involve phylogenetically ancient repair mechanisms. This is one of the reasons why therapeutic targeting of these mechanisms is difficult with the exception of life-style interventions which are, however, limited by individual compliance. In addition, the impact of many therapeutic agents on the entire organism is not well understood. Blood glucose control cannot be considered ?high tech“ medicine and requires non-medical personnel to reach defined blood glucose targets. Non-adherence to treatment and life-style changes, however, facilitate the interaction of patients and medical personnel and individuals with diabetes are therefore often considered themselves to ?blame“ for being affected by diabetes. Finally, generating treatment guidelines is extremely difficult as clinical studies targeting vascular endpoints need more than 10 years to become informative, partly due to the so-called glycaemic memory     

Lower Glycemic Fluctuations Early After Bariatric Surgery Partially Explained by Caloric Restriction

Background

We assessed the acute impact of laparoscopic Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG) compared to caloric-matched control group without surgery on glucose excursion in obese patients with type 2 diabetes, and examined if this was mediated by changes in insulin resistance, early insulin response or glucagon-like peptide (GLP)-1 levels.

Methods

Six-day subcutaneous continuous glucose monitoring (CGM) recordings were obtained from patients beginning 3 days before GBP (n?=?11), SG (n?=?10) or fasting in control group (n?=?10). GLP-1, insulin and glucose were measured during 75 g oral glucose tolerance testing at the start and end of each CGM.

Results

Post-operative hyperglycaemia occurred after both surgeries in the first 6 h, with a more rapid decline in glycaemia after GBP (p?<?0.001). Beyond 24 h post-operatively, continuous overlapping of net glycaemia action reduced from baseline after GBP (median [interquartile range]) 1.6 [1.2–2.4] to 1.0 [0.7–1.3] and after SG 1.4 [0.9–1.8] to 0.7 [0.7–1.0]; p?<?0.05), similar to controls (2.2 [1.7–2.5] to 1.3 [0.8–2.8] p?<?0.05). Higher log GLP-1 increment post-oral glucose occurred after GBP (mean ± SE, 0.80?±?0.12 vs. 0.37?±?0.09, p?<?0.05), but not after SG or control intervention. Among subgroup with baseline hyperglycaemia, a reduction in HOMA-IR followed GBP. Reduction in time and level of peak glucose and 2-h glucose occurred after both surgeries but not in controls.

Conclusions

GBP and SG have a similar acute impact on reducing glycaemia to caloric restriction; however, with a superior impact on glucose tolerance.     

Glycaemic responses to different carbohydrate foods in healthy and diabetic blacks in Soweto.

Diabetes mellitus is uncommon in rural southern African blacks. With urbanisation and lifestyle changes, incidence rises to that in western populations. To assess associated changes in carbohydrate metabolism, glycaemic responses to glucose, refined maize, refined rice and bread were studied in 8 healthy and 8 non-insulin-dependent diabetic urban blacks. Additionally, in the healthy group serum insulin responses were measured. In the healthy, maize (the staple food of blacks) elicited the highest glucose response (207 mmol/l/min) and bread the lowest (107 mmol/l/min). The glycaemic indices of maize and glucose were similar. Serum insulin responses to maize were significantly lower than that of bread at 90 minutes (maize 66 muU/ml; bread 93 muU/ml; P = 0.02). In diabetics, maize and glucose elicited similar glycaemia (928 mmol/l/min and 921 mmol/l/min respectively). The high glucose response to maize could relate to its processing and physical form. The low insulin secretion could be due to inadequate stimulation by the 'entero-insular' axis. Moreover, variability in glucose insulin responses could stem from ethnic or genetic reasons. In the dietary management of black diabetics, refined maize should be replaced by other cereals.     

Child health and health care utilisation. A community-based survey in Mitchell's Plain, CP

A community-based study of proxy-reported illness and health care use by children under 15 years of age in Mitchell's Plain, CP, is reported. The most commonly reported acute illness was respiratory infection and the most commonly reported chronic illness was asthma. There are estimated to be 1.82 consultations/child/year for acute illness. Fifty per cent of first-contact acute care was provided by private general practitioners. The public sector provided the remainder, and also care for the more severe acute illness and treated chronic illness. Medical aid was an important determinant of access to after-hours care. There is a need for an extended after-hours public sector service and similar studies elsewhere would be beneficial.     

Peri-operative management of patients with diabetes mellitus

Patients with diabetes mellitus are routinely encountered in anaesthetic practice. Peri-operative maintenance of good glycaemic control to avoid metabolic decompensation and its sequelae is considered to be the ideal, as they have a worse surgical outcome. In addition to routine anaesthetic assessment, patients with diabetes should be assessed pre-operatively for macrovascular complications (ischaemic heart disease, peripheral vascular disease, cerebrovascular disease) and microvascular complications (nephropathy, neuropathy, retinopathy) of diabetes, along with a review of overall glycaemic control. For elective surgery, patients with poor metabolic control should receive intensive glucose management. For major operations, patients will require an intravenous insulin infusion for which several regimens are currently used in clinical practice. The two most popular methods are: (1) the ‘sliding scale’ and (2) the GIK (glucose–insulin–potassium) infusion. Both methods have advantages and disadvantages, but for more complex surgery the ‘sliding scale’ method is more flexible. Minor surgery should not require the use of intravenous insulin infusions since these patients may be managed by adjustments in their usual dose of insulin or oral hypoglycaemic agents. In specific operative procedures, e.g. cardiothoracic surgery, major hyperglycaemic excursions have been shown to occur highlighting the need for stringent blood glucose monitoring.     

Coordinate changes in plasma glucose and pancreatic beta-cell function in Latino women at high risk for type 2 diabetes

The purpose of this study was to examine longitudinally the relationship among glucose levels, pancreatic beta-cell function, and insulin resistance in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and intravenous glucose tolerance tests (IVGTTs) were performed at 15-month intervals for up to 5 years or until fasting plasma glucose exceeded 140 mg/dl in Hispanic women with recent gestational diabetes. Data were analyzed 1) to compare changes in insulin sensitivity, beta-cell function, and glucose levels between women who had diabetes at one or more visits and women who remained diabetes free and 2) to determine longitudinal patterns of change in glucose levels and acute beta-cell compensation for insulin resistance. Seventy-one women provided data from a total of 280 paired OGTTs and IVGTTs during a median follow-up of 46 months. Compared with the 47 women who remained free of diabetes, the 24 who either had diabetes (n = 9) or developed it during follow-up (n = 15) had higher baseline glucose levels and lower acute beta-cell compensation for insulin resistance. Baseline insulin sensitivity was low in both groups and did not change significantly during follow-up. Fasting and 2-h glucose levels increased more rapidly in the diabetic group despite a decline in acute beta-cell compensation that was significantly slower than the decline in women who did not develop diabetes. This paradox was explained by an accelerated rise in glucose levels for any decline in beta-cell compensation when beta-cell compensation reached approximately 10% of normal, a level that was reached in the women who had or developed diabetes but not in the women who remained diabetes free. These findings define a pathogenesis for type 2 diabetes in one high-risk group that is characterized by a relatively long-term decline in acute beta-cell compensation for chronic insulin resistance that is attended by slowly rising glucose levels. Only relatively late in this process do glucose levels rise rapidly and into the diabetic range.     

Hyperglycemia in critically ill patients: clinical implications for treatment

Hyperglycemia is frequent during critical illness and is perceived by the clinician as part of the systemic metabolic response to stress. Of all patients with "stress hyperglycemia" only one third are known to have diabetes mellitus. Previous studies reported that patients presenting hyperglycemia during acute illness have an increased risk for nosocomial infections. Morbidity and mortality also increases in patients with myocardial infarction or stroke who develop hyperglycemia. Contemporary medical practice states that hyperglycemia under these conditions should only be treated with insulin if blood glucose levels are > 200 mg/dl. A recent trial showed that intensive insulin treatment of critically ill patients in the intensive care unit with the goal of maintaining blood glucose levels between 80 and 110 mg/dl significantly reduced morbidity and mortality without significant risk of hypoglycemia. These benefits of insulin treatment are not yet well understood, but some pathophysiological evidence suggests that hyperglycemia contributes to perpetuate the systemic proinflammatory response, and insulin--a natural endogenous hormone that has a major role in the intermediary metabolism--participates actively in the systemic anti-inflammatory response. As a result of these findings, we recommend that hyperglycemia during critical illness should be treated with insulin, in order to achieve blood glucose levels in a normal range, regardless of whether or not these patients have diabetes mellitus.     

Guar biscuits in the diabetic diet

A new type of guar-containing biscuit has been developed and incorporated into the diabetic diet in both short- and medium-term studies. It has been found to be effective in reducing the postprandial rise in the blood glucose level and in improving glycaemic control, as shown by reduced fasting blood glucose values and decreased 24-hour urinary glucose excretion. This form of guar has proved to be palatable and acceptable to patients. It was effective in smaller quantities than have previously been tested and may prove a valuable adjunct in the treatment of diabetes.     

Diabetes and cognitive function: An evidence-based current perspective

Several epidemiological studies have clearly identified diabetes mellitus (DM) as a major risk factor for cognitive dysfunction, and it is going to be a major public health issue in the coming years because of the alarming rise in diabetes prevalence across the world. Brain and neural tissues predominantly depend on glucose as energy substrate and hence, any alterations in carbohydrate meta-bolism can directly impact on cerebral functional output including cognition, executive capacity, and memory. DM affects neuronal function and mental capacity in several ways, some of which include hypoperfusion of the brain tissues from cerebrovascular disease, diabetes-related alterations of glucose transporters causing abnormalities in neuronal glucose uptake and metabolism, local hyper- and hypometabolism of brain areas from insulin resistance, and recurrent hypoglycemic episodes inherent to pharmacotherapy of diabetes resulting in neuronal damage. Cognitive decline can further worsen diabetes care as DM is a disease largely self-managed by patients. Therefore, it is crucial to understand the pathobiology of cognitive dysfunction in relation to DM and its management for optimal long-term care plan for patients. A thorough appraisal of normal metabolic characteristics of the brain, how alterations in neural metabolism affects cognition, the diagnostic algorithm for patients with diabetes and dementia, and the management and prognosis of patients when they have this dangerous combination of illnesses is imperative in this context. This evidence-based narrative with the back-up of latest clinical trial reviews elaborates the current understanding on diabetes and cognitive function to empower physicians to manage their patients in day-to-day clinical practice.     

Euglycemic diabetic ketoacidosis: A missed diagnosis

Euglycemic diabetic ketoacidosis(DKA) is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose(less than 11 mmol/L). The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units; it may delay diagnosis and treatment causing worse outcomes. Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus. With the addition of sodium/glucose cotransporter-2 inhibitors in diabetes mellitus management, euglycemic DKA incidence has increased. The other causes of euglycemic DKA include pregnancy, fasting, bariatric surgery, gastroparesis, insulin pump failure, cocaine intoxication, chronic liver disease and glycogen storage disease. The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit, milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio. Euglycemic DKA is a diagnosis of exclusion and should be considered in the differential diagnosis of a sick patient with a history of diabetes mellitus despite lower blood glucose or absent urine ketones. The diagnostic workup includes arterial blood gas for metabolic acidosis, serum ketones and exclusion of other causes of high anion gap metabolic acidosis. Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration, electrolytes deficit and insulin replacement. The dextrosecontaining fluids should accompany intravenous insulin to correct metabolic acidosis, ketonemia and to avoid hypoglycemia.     

Erythromycin promotes gastric emptying during acute pain in volunteers

In this double-blind cross-over study, we assessed whether erythromycin infusion is effective as a prokinetic drug against gastroparesis from acute pain. The effect of erythromycin on gastric emptying (GE) was measured in seven volunteers subjected to a standardized acute painful stimulus. The GE rate for solids was measured using the octanoic acid breath test. An acetaminophen absorption test measured the GE rate for liquids. Five minutes after ingestion of a 13C-labeled meal, the subjects received in randomized order either a test (placebo and erythromycin groups) or a control (control group) stimulus consisting of repeated 1-min immersion of a hand into 4 degrees C (test) or 37 degrees C (control) water, with 15 s for recovery between immersions, for a total of 20 min. While the stimulus was applied, 250 mL saline (control and placebo groups) or 250 mg erythromycin (erythromycin group) was infused. Pain and stress were evaluated using visual analog scales, and standard hemodynamic values were recorded throughout the study. Our results show that acute stress decreased GE for solids, which was significantly accelerated in the erythromycin group in comparison with the placebo group. GE for liquids was similar in the three groups. We conclude that erythromycin is effective as a prokinetic drug for solids in acute painful situations.     

Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy

The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs’ therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.     

Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion

As patients decline from health to type 2 diabetes, glucose-stimulated insulin secretion (GSIS) typically becomes impaired. Although GSIS is driven predominantly by direct sensing of a rise in blood glucose by pancreatic β-cells, there is growing evidence that hypothalamic neurons control other aspects of peripheral glucose metabolism. Here we investigated the role of the brain in the modulation of GSIS. To examine the effects of increasing or decreasing hypothalamic glucose sensing on glucose tolerance and insulin secretion, glucose or inhibitors of glucokinase, respectively, were infused into the third ventricle during intravenous glucose tolerance tests (IVGTTs). Glucose-infused rats displayed improved glucose handling, particularly within the first few minutes of the IVGTT, with a significantly lower area under the excursion curve within the first 10 min (AUC0-10). This was explained by increased insulin secretion. In contrast, infusion of the glucokinase inhibitors glucosamine or mannoheptulose worsened glucose tolerance and decreased GSIS in the first few minutes of IVGTT. Our data suggest a role for brain glucose sensors in the regulation of GSIS, particularly during the early phase. We propose that pharmacological agents targeting hypothalamic glucose-sensing pathways may represent novel therapeutic strategies for enhancing early phase insulin secretion in type 2 diabetes.