Glucagon Injection Research Articles

Rate of hypoglycemia in patients with type 2 diabetes receiving metformin plus saxagliptin versus metformin plus sulfonylurea: a retrospective observational cohort study using administrative claims data

Objectives: Hypoglycemia is a limiting factor in the management of diabetes. Studies comparing oral antidiabetic medications are needed to identify treatment options that can help clinicians and patients minimize their associated hypoglycemia risk. The purpose of this study was to compare hypoglycemia rates in patients with type 2 diabetes on metformin who initiated treatment with saxagliptin versus sulfonylurea (SU). Methods: This retrospective analysis utilized US healthcare claims data from the Truven Health MarketScan Research Databases. Data were from adults on metformin monotherapy who added saxagliptin or SU between 1 August 2009 and 31 December 2010. Hypoglycemia event rates were compared during the 4 months after initiation of saxagliptin or SU. A hypoglycemia event was defined as a diagnosis of hypoglycemia on an outpatient or emergency room claim, a principal diagnosis on a hospital claim, or a glucagon injection in an outpatient setting. Patients taking SU were matched to patients taking saxagliptin (5 to 1) using propensity scores, and the rate ratio was further adjusted using multivariate regression. A total of 22,592 patients (1567 taking saxagliptin; 21,025 taking SU) qualified. Results: During 120 days of follow-up, there were 396 hypoglycemia events. Most of the hypoglycemia events (91.9%) occurred in the outpatient setting. There were no inpatient or emergency room hypoglycemia events in the saxagliptin cohort. The overall unadjusted rate of hypoglycemia was significantly lower in the saxagliptin cohort than in the SU cohort (1.74 vs 5.58 per 100 person-years; p < 0.001). The rate of hypoglycemia also was significantly lower in the saxagliptin cohort versus the propensity-matched SU cohort (1.74 vs 4.45 per 100 person-years; p = 0.005). Matching reduced the treatment effect by approximately 20%. The rate ratio comparing saxagliptin with the unmatched and propensity-matched SU cohorts was 0.31 (95% CI: 0.14–0.6) and 0.39 (95% CI: 0.17–0.77), respectively. The multivariate adjustment decreased the hypoglycemia rate ratio 0.37 (95% CI: 0.19–0.74). Conclusion: In a database reflective of real-world clinical practice, saxagliptin had a lower risk of hypoglycemia than SU in patients with type 2 diabetes receiving metformin. These results add confidence to similar findings from clinical trials.

The influence of glucagon on the concentration of triacylglycerols and cholesterol in the liver and kidney of mice

Abstract. The experiment was performed on sexually mature male Swiss mice to determine the effect of pharmacological doses of glucagon administered over a period of 4 or 8 days on the concentration of triacylglycerols and cholesterol in liver and kidneys of mice selected for fast rate of body weight gain and unselected ones, kept on a high-protein and low-protein diet. On the basis of the results obtained it was concluded that the selection and the diet, as well as glucagon injections, were lowering the content of triacylglycerols and cholesterol in the examined organs of mice, in many cases confirmed in a statistically significant way.

Same Hormone, Different Actions

Glucagon signaling in the hypothalamus limits hepatic glucose production, rather than stimulating glucose production as this hormone does in the liver.

The incidence of severe hypoglycaemia in pregnant women with type 1 diabetes mellitus can be reduced with unchanged HbA1c levels and pregnancy outcomes in a routine care setting

AimsTo investigate whether the incidence of severe hypoglycaemia in pregnant women with type 1 diabetes can be reduced without deteriorating HbA1c levels or pregnancy outcomes in a routine care setting. MethodsTwo cohorts (2004–2006; n=108 and 2009–2011; n=104) were compared. In between the cohorts a focused intervention including education of caregivers and patients in preventing hypoglycaemia was implemented. Women were included at median 8 (range 5–13) weeks. Severe hypoglycaemia (requiring assistance from others) was prospectively reported in structured interviews. ResultsIn the first vs. second cohort, severe hypoglycaemia during pregnancy occurred in 45% vs. 23%, p=0.0006, corresponding to incidences of 2.5 vs. 1.6 events/patient-year, p=0.04. Unconsciousness and/or convulsions occurred at 24% vs. 8% of events. Glucagon and/or glucose injections were given at 15% vs. 5% of events. At inclusion HbA1c was comparable between the cohorts while in the second cohort fewer women reported impaired hypoglycaemia awareness (56% vs. 36%, p=0.0006), insulin dose in women on multiple daily injections was lower (0.77IU/kg (0.4–1.7) vs. 0.65 (0.2–1.4), p=0.0006) and more women were on insulin analogues (rapid-acting 44% vs. 97%, p<0.0001; long-acting 6% vs. 76%, p<0.0001) and insulin pumps (5% vs. 23%, p<0.0001). Pregnancy outcomes were similar in the two cohorts. ConclusionsA 36% reduction in the incidence of severe hypoglycaemia in pregnancy with unchanged HbA1c levels and pregnancy outcomes was observed after implementation of focused intervention against severe hypoglycaemia in a routine care setting. Improved insulin treatment, increased health professional education and fewer women with impaired hypoglycaemia awareness may contribute.

A Case of Type 1 Diabetes With Nocturnal Hypoglycemia After Desensitization Therapy for Insulin Allergy

Antibodies against exogenously injected insulin are common with insulin treatment but seldom have serious effects on blood glucose (1). In insulin autoimmune syndrome (IAS), however, the insulin antibody causes hypoglycemia (2) in the absence of exogenous insulin treatment. Here, we report a case of type 1 diabetes with insulin antibody, whereby the patient developed nocturnal hypoglycemia after desensitization therapy for an insulin allergy. After receiving insulin therapy for 1 year, a 61-year-old man was admitted to our hospital because of an insulin allergy and poor control of diabetes. He had an itchy eruption at the insulin injection site. At the time of admission, the patient presented with an HbA1c level of 16.2% (154 mmol/mol); anti-GAD antibody 80.0 U/L (<1.5 U/mL); serum C-peptide level 0.01 ng/mL after glucagon injection (fasting 0.67–2.48 ng/mL); and insulin-specific IgE 41.5 UA/mL (<0.34 …

Hypothalamic glucagon signaling inhibits hepatic glucose production

Glucagon activates hepatic protein kinase A (PKA) to increase glucose production, but the gluco-stimulatory effect is transient even in the presence of continuous intravenous glucagon infusion. Continuous intravenous infusion of insulin, however, inhibits glucose production through its sustained actions in both the liver and the mediobasal hypothalamus (MBH). In a pancreatic clamp setting, MBH infusion with glucagon activated MBH PKA and inhibited hepatic glucose production (HGP) in rats, as did central glucagon infusion in mice. Inhibition of glucagon receptor-PKA signaling in the MBH and hepatic vagotomy each negated the effect of MBH glucagon in rats, whereas the central effect of glucagon was diminished in glucagon receptor knockout mice. A sustained rise in plasma glucagon concentrations transiently increased HGP, and this transiency was abolished in rats with negated MBH glucagon action. In a nonclamp setting, MBH glucagon infusion improved glucose tolerance, and inhibition of glucagon receptor-PKA signaling in the MBH enhanced the ability of intravenous glucagon injection to increase plasma glucose concentrations. We also detected a similar enhancement of glucose concentrations that was associated with a disruption in MBH glucagon signaling in rats fed a high-fat diet. We show that hypothalamic glucagon signaling inhibits HGP and suggest that hypothalamic glucagon resistance contributes to hyperglycemia in diabetes and obesity.

Analysis of gene mutations and clinical manifestations in 20 patients with glycogen storage disease type Ia

Objective To investigate the glucose-6-phosphatese catalytic(G6PC) unit G6PC gene mutations in patients with liver glycogen storage disease(LGSD), and to discuss the relationship of glycogen storage disease type Ⅰa(GSDⅠa) genotype and phenotype. Methods According to clinical manifestations, laboratory tests and glucagon test results, 48 patients suspected as LGSD were selected in this research.By using PCR combined with direct DNA sequencing, the entire coding region of the G6PC gene was screened.Fifty healthy children were also investigated as control group.The species homology was analyzed by DNAMAN software to investigate gene conservatism. Results Eight types of G6PC gene mutations were detected in 20 cases of the 48 patients(41.67 %, 20/48 cases), which were c. 648G>T, p.R83H, p.H119L, p.L173P, p.I341N, c.260-262delGGinsA, p.C109Y and c. 260-262delGGinsA.Among which, c.648G>T and p. R83H were the common gene mutations in this study, their mutations frequency were 37.50% and 22.50%, respectively.p.C109Y and c. 260-262delGGinsA were novel mutations.All patients with different mutations had the same growth retardation, hypoglycemia, hepatomegaly, hyperlipidemia, lactic acidemia.Eighty-eight point twenty-four percent(15/17 cases) patients were hypoglycemia when fasted for 6 hours.The low blood sugar in 82.35%(14/17 cases) patients was no responsive to glucagon injection. Conclusions In this study, it revealed that c. 648G>T and p. R83H were the most common mutations in our patients.Two new pathogenic mutation types were found, which were p. C109Y and c. 260-262delGGinsA.The patients with different genotypes showed the same typical clinical manifestations. Key words: Glycogen storage disease type Ⅰa; Glucose-6-phosphatase; Gene mutation

Fibroblast Growth Factor 21 Mediates Specific Glucagon Actions

Glucagon, an essential regulator of glucose homeostasis, also modulates lipid metabolism and promotes weight loss, as reflected by the wasting observed in glucagonoma patients. Recently, coagonist peptides that include glucagon agonism have emerged as promising therapeutic candidates for the treatment of obesity and diabetes. We developed a novel stable and soluble glucagon receptor (GcgR) agonist, which allowed for in vivo dissection of glucagon action. As expected, chronic GcgR agonism in mice resulted in hyperglycemia and lower body fat and plasma cholesterol. Notably, GcgR activation also raised hepatic expression and circulating levels of fibroblast growth factor 21 (FGF21). This effect was retained in isolated primary hepatocytes from wild-type (WT) mice, but not GcgR knockout mice. We confirmed this link in healthy human volunteers, where injection of natural glucagon increased plasma FGF21 within hours. Functional relevance was evidenced in mice with genetic deletion of FGF21, where GcgR activation failed to induce the body weight loss and lipid metabolism changes observed in WT mice. Taken together, these data reveal for the first time that glucagon controls glucose, energy, and lipid metabolism at least in part via FGF21-dependent pathways.

Clinical, immunologic and insulin secretory characteristics of young black South African patients with diabetes: Hospital based single centre study

AimsTo classify and characterize the clinical features of various diabetes classes among young black South Africans. MethodsCross sectional study of 60 black patients with diabetes, all less than 30 years of age and attending Nelson Mandela Academic Hospital, Mthatha, South Africa. Diabetes was classified as Types 1A, 1B and 2 based on the anti-glutamic acid decarboxylase status and serum C-peptide response to intravenous injection of glucagon. ResultsMean age was 19.6±4.8 years (n=60) with similar gender distribution. The mean duration of diabetes was 24.2±45.1 months. Type 1A was the class of diabetes in 55% (n=33/60) of patients. Type 1B and 2 accounted for 30% (n=18/60) and 15% (n=9/60) of patients respectively. Patients classified as Type 2 had higher waist circumference and higher prevalence of acanthosis nigricans than Types 1A and 1B groups. History of diabetes in a first degree relative and hypertension were found in similar proportions of patients with Types 1A, 1B and 2 diabetes. Five Type 1A diabetes patients had body mass index of 26.2–41kg/m2 and this included two newly diagnosed patients with body mass index of 26.7kg/m2 and 33.2kg/m2. ConclusionThe majority of our young black South Africans with diabetes are of the Type 1A class. Acanthosis nigricans was not found in any patient with Type 1 A diabetes. A minority of Type 1 A diabetes patients were obese at initial diagnosis.

Increment of C-peptide after glucagon injection determines the progressive nature of Japanese type 2 diabetes: A long-term follow-up study

Type 2 diabetes (T2D) is characterized by a steady worsening of β-cell dysfunction as the disease progresses. The objective of this study was to estimate the decline of insulin secretion in Japanese type 2 diabetic patients (T2D-patients) by glucagon injection over an observation period of more than 10 years. Thirty-three T2D-patients were followed for 10.4 ± 1.4 years. Fasting C-peptide immunoreactivity (FCPR), the 6 min value of CPR after glucagon injection (6MCPR), and the increment of CPR (ΔCPR) were measured at baseline and follow-up. FCPR, 6MCPR, ΔCPR were significantly lower at follow-up than at baseline (p<0.05, p<0.005, and p<0.0005, respectively). The annual change of ΔCPR was significantly (p<0.05) greater than the annual change of FCPR (-0.062 ± 0.076 ng/mL/year and -0.025 ± 0.067 ng/mL/year, respectively). In contrast, CPR-index (an index of β-cell function) and SUIT-index (secretory units of islets in transplantation) calculated based on fasting blood samples were unaltered. The annual changes of FCPR, 6MCPR, and ΔCPR were negatively correlated with the FCPR, 6MCPR, and ΔCPR values at baseline, respectively. Duration of diabetes, BMI, diabetic retinopathy, and secondary sulfonylurea failure at baseline were not correlated with the annual changes of FCPR, 6MCPR, and ΔCPR. In conclusion, our longitudinal observations suggest that β-cell function progressively declines in Japanese T2D-patients. The annual declines of ΔCPR were more prominent than the annual declines of FCPR. ΔCPR after glucagon injection may be more useful for estimating individual longitudinal insulin secretion than fasting blood samples.

A retrospective study on the incidence and risk factors of severe hypoglycemia in primary care

To investigate the incidence and risk factors of severe hypoglycemia (SH) in primary care. SH was defined as hypoglycemia with coma, or the need of glucose or glucagon injection. We performed a cross-sectional retrospective study in patients with diabetes treated in primary care in Germany. We analyzed an unselected sample of participants with type 1 (n = 373) and type 2 diabetes (n = 4481) who participated in an insurance plan from the health care insurer Deutsche BKK. Data of participants with type 1 diabetes are as follows: women, n = 155 (42%); age, 49±16 years; diabetes duration, 20+13 years; BMI, 28±6 kg/m2; GHb, 7.1+1.5%; GHb≤7%, n = 263 (71%); GHb≥8.5%, n = 48 (13%). Data of participants with type 2 diabetes: women, n = 1979 (44%); age, 66±10 years; diabetes duration, 8±7 years; BMI, 30±5 kg/m2; GHb, 6.6±1.3%; GHb≤7%, n = 3747 (84%); GHb≥8.5%, n = 360 (8%); insulin therapy, n = 1175 (26%). The incidence of SH in type 1 diabetes: 1.3% (CI: 0.4%, 3.1%) per year; type 2 diabetes with insulin therapy: 0.9% (CI: 0.5%, 1.7%); without insulin therapy: 0.3% (CI: 0.1%, 0.6%). The event rate was 0.02 SH per patient/year in type 1 diabetes and 0.01 in type 2 diabetes, respectively. Low BMI, GHb, insulin therapy and female gender were associated with an increased risk of SH. In primary care, patients with diabetes can achieve good glycemic control with very rare events of SH. Due to low incidence, SH would have been an inappropriate parameter to evaluate the outcome quality of diabetes therapy in primary care.

Recurrent infantile hypoglycemia due to combined fructose-1,6-diphosphatase deficiency and growth hormone deficiency

A 14-month-old female infant presented with recurrent episodes of acute gastroenteritis accompanied by severe metabolic acidosis and hypoglycemia. Physical examination showed hepatomegaly. Laboratory evaluation revealed elevated hepatic enzymes, prolonged prothrombin time, hyperuricemia, and extremely elevated lactate and alanine levels. Glucagon injection during hypoglycemia resulted in a further decrease of blood glucose. She was treated with glucose-containing intravenous fluids, with rapid improvement and normalization of her blood pH and glucose levels. Hormonal assessment during two episodes of hypoglycemia indicated growth hormone (GH) deficiency. However, as isolated GH deficiency could not explain all other concomitant features, such as severe lactic acidosis, hepatomegaly, impaired liver function, and hyperuricemia, the possibility of a combined defect was suggested. Further lymphocytic enzymatic investigation revealed fructose-1,6-diphosphatase deficiency and molecular genetic analysis demonstrated frame shift mutation in the FBP1 gene. This enzyme deficiency causes a rare metabolic disorder not previously described in combination with GH deficiency.

Glucagon injection for type 1 diabetes in children

Glucagon has been prescribed routinely on diagnosis of paediatric type 1 diabetes. A forum of paediatric diabetes specialist nurses sought to examine whether this practice is evidence based. Forum members audited their own caseloads, including the families and carers, their professional practices and those of other teams nationally. It was found that the prescription of glucagon varies and its use is often limited by lack of confidence. They found little evidence to support routine prescription on diagnosis and recommend that individual case assessment of risk and of the needs and preferences of families and carers would be more cost effective. Families and carers who do acquire a glucagon injection kit should receive regular training in its use.

Glucagon injection for type 1 diabetes in children

Glucagon injection for type 1 diabetes in children

Congenital hyperinsulinism: current trends in diagnosis and therapy

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable.

The Effects of Insulin, Glucagon, Glutamate, and Glucose Infusion on Blood Glutamate and Plasma Glucose Levels in Naive Rats

Elevated levels of glutamate in brain fluids, in the context of several neurodegenerative conditions, are associated with a worsened neurological outcome. Because there is a clear relationship between brain glutamate levels and glutamate levels in the blood, and an association of the latter with stress, the purpose of this study was to investigate the effects of glucose, insulin, and glucagon on rat blood glutamate levels. Rats received either 1 mL/100 g of rat body weight (BW) intravenous isotonic saline (control), 150 mg/1 mL/100 g BW intravenous glucose, 75 mg/1 mL/100 g BW intravenous glutamate, 50 g/100 g BW intraparitoneal glucagon, or 0.2 UI/100 g BW intraparitoneal insulin. Blood samples were subsequently drawn at 0, 30, 60, 90, and 120 minutes for determination of blood glutamate and glucose levels. We observed a significant decrease in blood glutamate levels at 30 minutes after injection of glucose (P<0.05), at 30 and 60 minutes after injection of insulin (P<0.05), and at 90 and 120 minutes after injection of glucagon. Plasma glucose levels were elevated after infusion of glutamate and glucose but were decreased after injection of insulin. The results of this study demonstrate that glucose, insulin, and glucagon significantly reduce blood glutamate levels. The effect of insulin is immediate and transient, whereas the effect of glucagon is delayed but longer lasting, suggesting that the sensitivity of pancreatic glucagon and insulin-secreting cells to glutamate is dependent on glucose concentration. The results of this study provide insight into blood glutamate homeostasis and may assist in the implementation of new therapies for brain neuroprotection from excess glutamate.

Validation of a species‐optimized enzyme‐linked immunosorbent assay for determination of serum concentrations of insulin in dogs

Measurement of canine serum insulin has relied on methods developed to measure human insulin. A species-optimized test for measurement of serum insulin in dogs is now commercially available. The purpose of this study was to validate the canine ELISA for determination of serum insulin concentration in dogs. Precision was determined by evaluating intra- and interassay coefficient of variation (CV), and accuracy was determined by dilution and spike recovery studies. A method comparison study with samples from 34 clinically healthy dogs and 73 dogs examined for various illnesses and disorders ("patients") was performed using the canine ELISA and an ELISA for human insulin. Biologic relevance of the canine assay was evaluated by measuring insulin in samples collected from 8 healthy dogs after administration of glucagon. A stability study was preformed with 6 samples stored at 20°C, 4-8°C, and -20°C. For the canine ELISA, intra- and interassay CVs were 4.3-7.8% and 4.4-7.7%, respectively. Mean recovery after dilution was 99% and recovery after spiking with porcine insulin was 116%. The canine and human ELISAs correlated well (r(2) =.94 for healthy dogs, r(2) =.88 for patient samples). After glucagon injection serum insulin concentrations increased significantly in 8 dogs. Insulin was stable for 30 days in 6 serum samples stored at -20°C and in most samples for 8 days at 4-8°C. Insulin was stable for <3 days at room temperature (20°C). The new canine serum insulin ELISA had good precision and accuracy and correlated well with the previously used assay.

Progressive deterioration of insulin secretion in Japanese type 2 diabetic patients in comparison with those who carry the S20G mutation of the islet amyloid polypeptide gene: A long-term follow-up study.

Aims/Introduction: In order to clarify the enhanced β-cell dysfunction in type 2 diabetic patients carrying the S20G mutation of the islet amyloid polypeptide gene (S20G-patients), we first estimated the decline of insulin secretion in Japanese type 2 diabetic patients without the S20G mutation (non-S20G-T2D-patients) by long-term observation, and then compared it with that of the S20G-patients. We followed 70 non-S20G-T2D-patients (body mass index <30 kg/m(2)) for more than 10 years and six S20G-patients for more than 5 years. We measured fasting C-peptide (F-CP) every 1-2 years and carried out a glucagon test at least once during the follow-up period. F-CP and a 5-min value of C-peptide after glucagon injection (5'-CP) were used as the indices of insulin secretion. We excluded patients who had renal dysfunction and/or anti-insulin antibodies in the insulin-treated patients. The individual annual declines were calculated from the slopes of the regression lines between C-peptide levels and duration (years after diagnosis). The mean individual annual declines of both F-CP and 5'-CP were significantly greater in the S20G-patients than the non-S20G-T2D-patients (F-CP; 0.047 ± 0.026 vs 0.011 ± 0.037 nmol/L/year, P = 0.025, 5'-CP; 0.139 ± 0.055 vs 0.022 ± 0.012 nmol/L/year, P = 0.008). We established the annual decline of insulin secretion in the Japanese type 2 diabetic patients by the long-term observation. The results show that the decline of insulin secretion is more rapid in the S20G-patients than the non-S20G-T2D-patients. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00102.x, 2011).

Transient Efficacy of Octreotide and Pasireotide (SOM230) Treatment in GIP-dependent Cushing's Syndrome

We studied a 55-year old woman presenting with features of Cushing's syndrome associated with metabolic abnormalities including severe hypertension and type 2 diabetes. Urinary free cortisol excretion was within normal limits, but an unusual diurnal cortisol rhythm was observed with low morning and high postprandial levels, associated with the absence of cortisol suppression after dexamethasone, suggesting the possibility of GIP-dependent Cushing's syndrome. The diagnosis was confirmed by further investigations, showing significant plasma cortisol responses after a mixed meal test and after oral, but not intravenous glucose administration, as well as ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). An aberrant increase in cortisol was also observed after glucagon and terlipressin injections. The patient was first treated with octreotide 100-250 μg thrice daily for 6 months, then with the new multi-ligand somatostatin analogue (SOM 230) 450-900 μg twice daily for 3 months. Although inducing a significant acute suppression of post-prandial cortisol response, both drugs had no effects on the clinical and metabolic abnormalities associated with Cushing's syndrome and new tests performed at the end of each treatment period confirmed escape of post-meal cortisol suppression to therapy. The patient finally underwent a bilateral adrenalectomy, which markedly improved her medical condition and allowed in vitro confirmation by real time RT-PCR quantification of a high aberrant expression of GIP receptor mRNA in adrenal tissue. This case report illustrates the lack of sustained efficacy of somatostatin analogues on GIP-dependent Cushing's syndrome, independent of their affinity for the different somatostatin receptor subtypes.

Utility of indices using C-peptide levels for indication of insulin therapy to achieve good glycemic control in Japanese patients with type 2 diabetes.

Aims/Introduction: Type 2 diabetes is progressive in that therapy must be altered over time, which is partly as a result of the progressive loss of pancreatic β-cell function. To elucidate the relationship between residual endogenous insulin secretion and the necessity of insulin therapy to achieve good glycemic control, indices using serum C-peptide immunoreactivity (CPR) were analyzed in patients with type 2 diabetes. The data of 201 Japanese patients with type 2 diabetes who achieved the target of glycemic control during admission were analyzed retrospectively. Indices using CPR including fasting CPR (FCPR), CPR 6 min after intravenous injection of glucagon (CPR-6 min), increment of CPR (ΔCPR), secretory unit of islet in transplantation index (SUIT) and C-peptide index (CPI) were compared between the group requiring insulin (insulin group) and the group not requiring insulin (non-insulin group). A receiver-operator characteristic (ROC) curve was made, and optimal cut-off point and likelihood ratio were determined for each index. All indices of CPR were lower in the insulin group compared with those in the non-insulin group. Likelihood ratios at the optimal point of FCPR, CPR-6 min, ΔCPR, SUIT, and CPI were 2.0, 2.1, 1.6, 2.3 and 2.8, respectively. Optimal cut-off point of CPI was 1.1 ng/mg. Sensitivity and specificity at optimal point of CPI were 61 and 78%, respectively. The advantage of CPI of the indices of CPR to select insulin therapy to achieve good glycemic control was shown, but limitations of the predictive abilities of the indices using CPR should be taken into account. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00096.x, 2011).