Improved Glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy ((1)H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA(1c) reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (-59.3, -16.5%). The relative reduction in IHL correlated with that in HbA(1)c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism

Isolated thyroxine malabsorption treated with intramuscular thyroxine injections

An 18-year-old girl with multiple autoimmune endocrinopathies was referred to the endocrinology clinic for management of hypothyroidism. She required increasing doses of thyroxine but remained hypothyroid. Daily and weekly supervised thyroxine administration strategies were unsuccessful. She was extensively investigated for malabsorption; however, all the results were normal. She was subsequently commenced on weekly intramuscular thyroxine injections and became biochemically and clinically euthyroid. Subsequent elective hospital admission and administration of thyroxine via nasogastric tube resulted in recurrence of her hypothyroidism. This case demonstrates apparent isolated true levothyroxine malabsorption existing in isolation and suggests that intramuscular thyroxine injections may be a useful therapeutic modality in these patients

Thiazolidinediones and the renal and hormonal response to water immersion-induced volume expansion in type 2 diabetes mellitus

Thiazolidinediones cause sodium retention and edema by a direct effect on the kidneys. The aim of this study was to use the technique of head-out water immersion to investigate the effects of rosiglitazone on sodium and volume homeostasis in subjects with type 2 diabetes mellitus. The volume expansion response to water immersion was compared with the response on a non-immersion control day in 12 nondiabetic male subjects and 8 diet-controlled male type 2 diabetic subjects with hourly blood and urine sampling over a 4-h period. This was repeated after both groups had taken 4 mg of rosiglitazone daily for 7 days. Immersion produced a natriuresis in both groups (P < 0.001). An impairment of this natriuresis was seen in the diabetic subjects (P = 0.006). However, when rosiglitazone was taken, there was no significant difference in immersion-induced natriuresis compared with nondiabetic controls (P = 0.2). There was an immersion-induced rise in atrial natriuretic peptide (ANP) and urinary cyclic guanosine monophosphate (cGMP), in the healthy subjects (ANP P = 0.001, cGMP P = 0.043), which was not seen in the diabetic subjects (ANP P = 0.51, cGMP P = 0.74). Rosiglitazone restored the immersion-induced increase in cGMP excretion and rise of ANP in the diabetic group (ANP P = 0.048, cGMP P = 0.009). This study confirms that type 2 diabetic subjects have an impaired natriuretic response to acute volume expansion, which appears to be enhanced rather than diminished by rosiglitazone. This may be related to its effects in increasing natriuretic peptides and restoring the impaired cGMP excretion to volume expansion

Identifying women with persistent abnormal glucose metabolism following gestational diabetes mellitus: Changing times, changing populations and changing needs

Introduction: An oral glucose tolerance test (OGTT) six weeks after delivery is considered the gold standard test to identify persistently abnormal glucose metabolism in women with gestational diabetes mellitus (GDM) but the National Institute for Health and Clinical Excellence (NICE) recommends fasting plasma glucose (FPG) alone. This however, cannot be used to diagnose those with persisting impaired glucose tolerance and will also fail to identify some women with persisting diabetes mellitus (DM). This study aims to identify the percentage of women with DM and impaired glucose tolerance (IGT) that would be missed using this strategy. Methods: Data from 147 women from two sites were analysed. Fishers’ exact test was used to demonstrate differences between OGTT and FPG and a receiver operating characteristic curve was used to try and identify a FPG concentration that would predict a post-glucose load abnormality. Results: Fifty-two of the 147 women had a persistent abnormality in glucose metabolism. Twenty-three had impaired fasting glycaemia (IFG), 21 had IGT and eight women had DM. Only seven of the eight women with DM had a FPG ≥ 7.0 mmol/L and hence one out of eight women with DM (12.5%) and all 21 women with IGT would have been missed if FPG alone were used (p&lt;0.001). Conclusion: Postnatal FPG alone is inadequate to identify all women with DM and would miss a significant number of women with IGT. An OGTT in all women with diagnosed GDM remains the gold standard test to identify persistent abnormal glucose metabolism in these women. </jats:sec

<i>Upper:</i> Relative changes in liver fat related to relative change in HbA₁c (ρ = 0.49; p = 0.01) (left) and absolute change in liver fat related to absolute change in HbA₁c (ρ = 0.38; p = 0.06) (right).

<p><i>Lower:</i> Relative changes in liver fat related to relative change in weight (ρ = 0.21; p = 0.31) (left) and absolute change in liver fat related to absolute change in weight (ρ = −0.04; p = 0.86) (right).</p

<i>Upper</i> Change in liver fat according to weight loss of <5% and >5% and according to relative reduction in HbA1c above or below median (median absolute reduction in HbA1c = 1.3%).

<p><i>Lower:</i> Change in liver fat according to pre-treatment liver fat percentage (left) and individual plots to demonstrate changes in liver fat ranked by pre-treatment liver fat percentage (right).</p

Correlation between changes in liver fat (%) and: <i>Upper:</i> change in total abdominal fat (litres).

<p><i>Middle:</i> change in abdominal subcutaneous fat (litres). <i>Lower:</i> change in intra-abdominal visceral fat (litres).</p

Starvation-induced True Diabetic Euglycemic Ketoacidosis in Severe Depression

True euglycemic diabetic ketoacidosis [blood glucose <200 mg/dl (11.1 mmol/l)] is relatively uncommon and in type 1 diabetes can be caused by starvation of any cause in conjunction with an intercurrent illness. We report a case of euglycemic diabetic ketoacidosis precipitated by starvation resulting from severe depression in a patient with type 1 diabetes. He was acidotic with ketonuria, but his blood glucose was only 105 mg/dl (5.8 mmol/l). He was rehydrated, the acidosis was corrected, and his depression was later treated. This case involves the complex interplay among type 1 diabetes, depression, ketoacidosis, and starvation physiology resulting in glucose concentrations in keeping with euglycemic diabetic ketoacidosis. The case also highlights that even in the absence of hyperglycemia, acid/base status should be assessed in an ill patient with diabetes, and in cases of euglycemic diabetic ketoacidosis, the diagnosis of depression should be considered as a cause for suppressed appetite and anorexia