Cardiovascular Safety of Gla-100: Reflections From the ORIGIN and ORIGINALE Trials.

Cardiovascular diseases (CVD) risk in people with type 2 diabetes mellitus (T2DM) is two to four folds higher than in individuals without T2DM. Insulin therapy was speculated to be atherogenic- thereby aggravating CVD risk years ago. However, cardiovascular outcome trials (CVOTs) such as the Outcome Reduction with Initial Glargine Intervention (ORIGIN), and its extended follow-up study - ORIGIN and Legacy Effects (ORIGINALE) conclusively established the long-term cardiovascular (CV) safety of basal insulin, such as insulin glargine 100 U/mL (Gla-100). Moreover, these studies hinted at the possible benefits of early insulin therapy-including stalling the progression of diabetes with minimal weight gain and hypoglycemia risk. This review highlights the background developments which led to the ORIGIN trial. Additionally, it also dwells on the critical insights to emerge from this trial pertaining to the CV safety of basal insulin Gla-100 in high CV risk individuals with T2DM.

Podocin and beta dystroglycan expression to study podocyte-podocyte and basement membrane matrix connections in adult protienuric states.

BACKGROUND: Podocytes can be the primary site of injury or secondarily involved in various protienuric states. Cross talk between adjacent foot processes and with basement membrane is important for slit diaphragm function. Does expression of podocyte associated proteins in kidney biopsies alter with site/type of primary injury? Genetic mutations of podocin result in steroid resistant FSGS. Can protein expression of podocin predict resistant cases to initiate further genetic evaluation? METHODS: Adult patients (n-88) with protienuria- minimal change disease(MCD)-22, focal segmental glomerulosclerosis(FSGS)-21,membranous glomerulonephritis(MGN)-25 and IgA nephropathy(IgAN)-20 were selected for immunohistochemistry with podocin and beta dystroglycan . Results were graded (0 - 3+scale )and compared with control biopsies and internal control. Treatment and follow up (6 months -2 ½ years) of FSGS and MCD cases were collected. RESULTS: There was intense to moderate staining of the podocytes with podocin and ß dystroglycan in the glomeruli in all cases (MCD, FSGS, IgAN and MGN) except for weak staining with ß dystroglycan in 3 cases of MCD. There was loss of immunostains in areas of segmental/global sclerosis. There was no significant difference in the staining pattern between the groups. In primary podocytopathies, staining pattern did not differ between steroid resistant, sensitive or dependent cases. CONCLUSIONS: Immunohistochemical expression of podocin and ß dystroglycan does not differ in nephropathies which have different site of injury depending on absence (MCD and FSGS) or presence of immune deposits and their localization (MGN and IgAN). Podocin and ß dystroglycan staining did not differentiate steroid sensitive and resistant cases, hence, does not give clue to initiate genetic studies. However, analysis of bigger cohort may be required. SUMMARY: Podocin and ß dystroglycan immunohistochemistry was done to analyze podocyte - podocyte and podocyte -basement membrane matrix connections in adult protienuric states. Primary podocytopathies i.e. MCD and FSGS and secondary podocytopathy due to immune complex deposition, i.e., MGN (subepithelial) and IgAN (mesangial) were analyzed. There was no difference in staining patterns between primary and secondary podocytopathies or between steroid sensitive, resistant and dependent cases of FSGS and MCD. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2258608781052786.

(18)F-FDG PET/CT in bilateral primary adrenal T-cell lymphoma.

Primary adrenal lymphoma is extremely rare. We report a young patient who presented with non- specific symptoms of fever and abdominal pain. Conventional imaging modalities demonstrated bilateral bulky adrenal masses, and whole-body fluorine-18-fluorodesoxyglucose ((18)F-FDG) positron emission tomography/computed tomography showed intense (18)F-FDG-avid bilateral adrenal masses with no evidence of extra-adrenal spread. A pathological diagnosis of non-Hodgkin lymphoma of peripheral T-cell type was made. The present case indicates that primary adrenal lymphoma should be included in the differential diagnosis of bilateral adrenal masses.

The prevalence of syndrome Z (the interaction of obstructive sleep apnoea with the metabolic syndrome) in a teaching hospital in Singapore.

BACKGROUND: Syndrome Z describes the interaction of obstructive sleep apnoea (OSA) with the metabolic syndrome. PURPOSE OF STUDY: A pilot study to determine the prevalence of syndrome Z in a teaching hospital in Singapore. METHODS: Patients (age > or =18 years) recruited for this prospective study had to satisfy three of the following five inclusion criteria: fasting glucose >6.1 mmol/l, blood pressure >/=130/85 mm Hg, HDL cholesterol <1.04 mmol/l in men and <1.2 mmol/l in women, triglycerides > or =1.7 mmol/l, and a waist circumference >102 cm in men and >88 cm in women. All subjects underwent standard overnight polysomnography. Overnight fasting glucose and lipid levels were measured and baseline anthropometric data recorded. All sleep studies were scored and reported by a sleep physician. OSA was deemed to be present if the respiratory disturbance index (RDI) was > or =5, with mild, moderate and severe categories classified according to the Chicago criteria. RESULTS: There were 24 patients (19 males and five females) of whom 10 were Chinese, eight Malay and five of Indian origin, with one other. Mean age was 48+/-13.5 years, mean body mass index was 34.9+/-6.1 kg/m2 and mean waist circumference was 111.3+/-15.7 cm. 23 (95.8%) of the patients had OSA with a mean RDI of 39.6+/-22.4 events/h with 15 patients (62.5%) in the severe category. The five patients who fulfilled all five criteria for diagnosis of the metabolic syndrome had severe OSA. CONCLUSION: The prevalence of OSA in our studied population exhibiting the metabolic syndrome is very high. Therefore, a polysomnogram should always be considered for this subset of patients.