Comparative efficacy and safety of two fixed ratio combinations in type 2 diabetes mellitus patients previously poorly controlled on different insulin regimens: a multi-centric observational study.

OBJECTIVE: To evaluate the efficacy and safety profile of fixed ratio combinations (FRC) in patients with type 2 diabetes mellitus (DMT2) poorly controlled on different insulin regimens. PATIENTS AND METHODS: This multicentric observational study included 376 patients (157 males, 219 female), with longstanding DMT2 inadequately controlled (HbA1c >7%) on different insulin regimens; premix insulin analogs (MIX) (23.2%), basal-bolus regimen (BB) (30.9%) or basal oral therapy (BOT) (37.1%) to whom FRC was introduced at least 6 months prior to data collection. RESULTS: Median age of patients was 67 years, with the duration of diabetes for 14 years, median HbA1c of 8.4% and BMI of 34.35 kg/m2. The proportion of patients treated with IDegLira and IGlarLixi was similar (48.4% vs. 51.6%). There was a borderline difference regarding regimen groups (p = 0.059) implying the greatest improvement of HbA1c in the MIX group. The significant interaction between BOT and BB/MIX regimens (p = 0.011) was noted indicating the largest reduction of BMI in BB and MIX groups. After the FRC administration, there was no significant difference in gastrointestinal (GIT) side-effects. The number of patients with hypoglycemic episodes decreased from 24% to 7% after FRC initiation (p < .001). The group using IGlarLixi required a significantly higher average dose steps compared to IDegLira (p < .001 for all) to achieve glycemic goals, while a larger proportion of patients using IDegLira lost more than 5 kg, compared to IGlarLixi (p < .001). Significant improvement was observed in all glycemic parameters in all insulin treated patients after replacement of insulin therapy with FRC (p < .001 for all). Composite outcome defined as any weight loss and HbA1c below 7% was accomplished in 20.3% of patients. CONCLUSIONS: In real life setting switching to both FRC options in people with longstanding inadequately controlled DMT2 treated with different insulin regimens could offer an effective therapeutic choice for achieving glycemic goals, with an improved safety profile.

Regional variations in definitions and rates of hypoglycaemia: findings from the global HAT observational study of 27 585 people with Type 1 and insulin-treated Type 2 diabetes mellitus.

AIM: To determine participant knowledge and reporting of hypoglycaemia in the non-interventional Hypoglycaemia Assessment Tool (HAT) study. METHODS: HAT was conducted in 24 countries over a 6-month retrospective/4-week prospective period in 27 585 adults with Type 1 or insulin-treated Type 2 diabetes mellitus. Participants recorded whether hypoglycaemia was based on blood glucose levels, symptoms or both. RESULTS: Hypoglycaemia rates were consistently higher in the prospective compared with the retrospective period. Most respondents (96.8% Type 1 diabetes; 85.6% Type 2 diabetes) knew the American Diabetes Association/European Association for the Study of Diabetes hypoglycaemia definition, but there were regional differences in the use of blood glucose measurements and/or symptoms to define events. Confirmed symptomatic hypoglycaemia rates were highest in Northern Europe/Canada for Type 1 diabetes (63.9 events/year) and in Eastern Europe for Type 2 diabetes (19.4 events/year), and lowest in South East Asia (Type 1 diabetes: 6.0 events/year; Type 2 diabetes: 3.2 events/year). Unconfirmed symptomatic hypoglycaemia rates were highest in Eastern Europe for Type 1 diabetes (5.6 events/year) and South East Asia for Type 2 diabetes (4.7 events/year), and lowest for both in Russia (Type 1 diabetes: 2.1 events/year; Type 2 diabetes: 0.4 events/year). Participants in Latin America reported the highest rates of severe hypoglycaemia (Type 1 diabetes: 10.8 events/year; Type 2 diabetes 3.7 events/year) and severe hypoglycaemia requiring hospitalization (Type 1 diabetes: 0.56 events/year; Type 2 diabetes: 0.44 events/year). The lowest rates of severe hypoglycaemia were reported in South East Asia (Type 1 diabetes: 2.0 events/year) and Northern Europe/Canada (Type 2 diabetes: 1.3 events/year), and the lowest rates of severe hypoglycaemia requiring hospitalization were in Russia (Type 1 diabetes: 0.15 events/year; Type 2 diabetes: 0.09 events/year). The blood glucose cut-off used to define hypoglycaemia varied between regions (Type 1 diabetes: 3.1-3.6 mmol/l; Type 2 diabetes: 3.5-3.8 mmol/l). CONCLUSIONS: Under-reporting of hypoglycaemia rates in retrospective recall and regional variations in participant definitions of hypoglycaemia may contribute to the global differences in reported rates. Discrepancies between participant definitions and guidelines may highlight a need to redefine hypoglycaemia criteria. (Clinical Trials Registry No: NCT01696266).

Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: the global HAT study.

AIMS: To determine the global extent of hypoglycaemia experienced by patients with diabetes using insulin, as there is a lack of data on the prevalence of hypoglycaemia in developed and developing countries. METHODS: This non-interventional, multicentre, 6-month retrospective and 4-week prospective study using self-assessment questionnaire and patient diaries included 27 585 patients, aged ≥18 years, with type 1 diabetes (T1D; n = 8022) or type 2 diabetes (T2D; n = 19 563) treated with insulin for >12 months, at 2004 sites in 24 countries worldwide. The primary endpoint was the proportion of patients experiencing at least one hypoglycaemic event during the observational period. RESULTS: During the prospective period, 83.0% of patients with T1D and 46.5% of patients with T2D reported hypoglycaemia. Rates of any, nocturnal and severe hypoglycaemia were 73.3 [95% confidence interval (CI) 72.6-74.0], 11.3 (95% CI 11.0-11.6) and 4.9 (95% CI 4.7-5.1) events/patient-year for T1D and 19.3 (95% CI 19.1-19.6), 3.7 (95% CI 3.6-3.8) and 2.5 events/patient-year (95% CI 2.4-2.5) for T2D, respectively. The highest rates of any hypoglycaemia were observed in Latin America for T1D and Russia for T2D. Glycated haemoglobin level was not a significant predictor of hypoglycaemia. CONCLUSIONS: We report hypoglycaemia rates in a global population, including those in countries without previous data. Overall hypoglycaemia rates were high, with large variations between geographical regions. Further investigation into these differences may help to optimize therapy and reduce the risk of hypoglycaemia.

nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma.

BACKGROUND: The discovery that genetic alterations in oncogenes and tumour suppressor genes accompany tumour formation in many human tumours has encouraged the search for genes that promote or suppress tumour spread and metastasis; nm23 is a promising candidate for a metastasis suppressing gene. AIMS: To evaluate whether expression of nm23-H1 protein or loss of heterozygosity (LOH) of the nm23-H1 gene is associated with colon cancer progression. MATERIALS/METHODS: Paraffin wax embedded tissue sections were analysed immunohistochemically. DNA isolated from normal and tumour tissue was used for LOH analysis using a variable nucleotide tandem repeat (VNTR) marker located in the untranslated 5' region of the nm23-H1 gene. RNA isolated from tumour and normal tissue was used for "real time" RT-PCR. RESULTS: Of 102 adenocarcinomas examined, 58.8% stained weakly for nm23-H1 protein. There was a negative correlation between nm23-H1 positivity and tumour histological grade. In VNTR analysis, 70.2% of patients were informative and 27.4% of tumours had nm23-H1 LOH. There was a positive correlation between nm23-H1 LOH and both tumour histological grade and Dukes's stage. Expression of nm23-H1 mRNA was increased in 22 of 30 colon tumours compared with normal tissue. No significant correlation was found between nm23-H1 mRNA expression and histological grade or Dukes's stage of tumours. CONCLUSIONS: These findings suggest that nm23-H1 protein expression in early stages may have a role in suppressing metastasis in sporadic colon cancer, whereas at a later stage both reduced nm23-H1 protein expression and LOH of the nm23-H1 gene may play role in colon cancer progression and metastasis.

Chiasma syndrome in acromegalic patients--correlation of neuroradiologic and neuroophthalmologic findings.

The study evaluated neuroophthalmologic and computerized tomography (CT) findings in 100 patients with somatotrophic adenoma and clinical picture of acromegaly, who underwent transsphenoidal adenomectomy. Prior to the surgery, visual field was normal in 77 patients. The diameter of adenoma in these patients ranged from 8 to 30 mm on CT, and the average value was 13.5 mm. Various kinds of visual field disturbances were present in 23 patients. The diameter of their adenomas ranged between 18 to 35 mm, with the average of 24.7 mm. Compared to visual field defects, CT findings of suprasellar adenoma extension were better correlated with chiasma syndrome (p < 0.001). All patients with suprasellar mass greater than 10 mm had chiasma syndrome. Degenerative adenoma changes (hemorrhagic necrosis), which precipitate abrupt increase in size of the tumor, were more frequently seen in patients with chiasma syndrome. The incidence of chiasma syndrome directly correlates with the degree of suprasellar extension of the tumor.

Diagnostic value of thyrotropin releasing hormone test in 129 patients with suspected tumoral hyperprolactinemia.

In 129 hyperprolactinemic (PRL > or = 100 ng/mL) and 100 normoprolactinemic patients (PRL 0-25 ng/mL), delta max. PRL (the difference between maximal prolactin (PRL) after thyrotropin releasing hormone (TRH) injection and basal value) was compared with basal PRL and computed tomography (CT) of the sellar region. In 122 hyperprolactinemic patients delta max. PRL was < 100%, while tumor was found in 106 of them. In the remainder seven hyperprolactinemic patients delta max. PRL was > or = 100% and CT showed no tumor. A significant difference in delta max. PRL between hyperprolactinemic patients without and those with verified adenoma was found and showed a significant negative correlation with basal PRL. Between 122 hyperprolactinemic patients with delta max. PRL < 100%, mean basal PRL and duration of clinical symptoms were significantly lower in 16 patients with normal CT compared to 106 patients with tumor. All normoprolactinemic patients showed delta max. PRL > or = 100% and no tumor on CT. PRL stimulation disturbance precedes tumor visualization and represents a decisive diagnostic parameter in hyperprolactinemic patients with no tumor signs.

Lymphocytic adenohypophysitis simulating a pituitary adenoma in a pregnant woman.

The lymphocytic hypophysitis, appearing in women during the third trimester of pregnancy or early post-partum period, is a rare cause of hypopituitarism and pituitary enlargement. A 39 year-old woman presented in the 37th week of pregnancy with bilateral heteronymous quadrantanopsia, CT indicative of tumorous mass and symptoms of hypopituitarism with decreased thyroid hormone and thyrotrophin levels, and low normal level of cortisol. After the birth of a healthy male child the patient breastfed for 10 days, sight disturbances disappeared, but amenorrhea persisted. Upon admittance the visual field showed no abnormalities. MR of the sellar region confirmed previous CT findings. Endocrinological testing confirmed secondary hypothyroidism and cortisol deficiency, normal levels of prolactin with satisfactory reaction to thyroliberin. Histology showed mononuclear infiltration, and immunohistochemistry revealed T-cells (CD3) at the borders, and B-cells (CD20) in the follicular center. Due to enlargement of the pituitary associated with hypopituitarism, an incorrect diagnosis of a tumor could be made.

Neuroendocrinological aspects of primary empty sella.

Neuroendocrinological aspects of 42 patients (33 women, 9 men) with primary empty sella confirmed by CT, cysternography and/or MR imaging were analyzed. The prominent symptoms were headache, visual disturbances and hypertension, occurring primarily in obese women (84.5%). Patients underwent dynamic endocrine testing consisting of insulin-induced hypoglycemia and anterior pituitary stimulation tests GnRH and TRH. Variable degree of pituitary dysfunction was observed in 28 (66.6%) patients. In this study 20 (47.6%) patients were presented with latent hypopituitarism, while manifest hypopituitarism, requiring replacement therapy, occurred in 8 (19%) patients. Mild hyperprolactinaemia was found in 3 patients. Even 14 (33.3%) patients had no evidence of endocrine dysfunction. Often mentioned diabetes insipidus and rhinoliquorrhea were not reported in this study.