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Ajay Varanasi, Natalie Bellini, Deepti Rawal, Mehul Vora, Antoine Makdissi, Sandeep Dhindsa, Ajay Chaudhuri and Paresh Dandona


To determine whether the addition of liraglutide to insulin to treat patients with type 1 diabetes leads to an improvement in glycemic control and diminish glycemic variability.

Subjects and methods

In this study, 14 patients with well-controlled type 1 diabetes on continuous glucose monitoring and intensive insulin therapy were treated with liraglutide for 1 week. Of the 14 patients, eight continued therapy for 24 weeks.


In all the 14 patients, mean fasting and mean weekly glucose concentrations significantly decreased after 1 week from 130±10 to 110±8 mg/dl (P<0.01) and from 137.5±20 to 115±12 mg/dl (P<0.01) respectively. Glycemic excursions significantly improved at 1 week. The mean s.d. of glucose concentrations decreased from 56±10 to 26±6 mg/dl (P<0.01) and the coefficient of variation decreased from 39.6±10 to 22.6±7 (P<0.01). There was a concomitant fall in the basal insulin from 24.5±6 to 16.5±6 units (P<0.01) and bolus insulin from 22.5±4 to 15.5±4 units (P<0.01).

In patients who continued therapy with liraglutide for 24 weeks, mean fasting, mean weekly glucose concentrations, glycemic excursions, and basal and bolus insulin dose also significantly decreased (P<0.01). HbA1c decreased significantly at 24 weeks from 6.5 to 6.1% (P=0.02), as did the body weight by 4.5±1.5 kg (P=0.02).


Liraglutide treatment provides an additional strategy for improving glycemic control in type 1 diabetes. It also leads to weight loss.

Free access

Husam Ghanim, Sandeep Dhindsa, Sanaa Abuaysheh, Manav Batra, Nitesh D Kuhadiya, Antoine Makdissi, Ajay Chaudhuri and Paresh Dandona


One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression.

Materials and methods

This is a randomized double-blind placebo-controlled trial. Thirty-two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ERα and aromatase expression in peripheral blood mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and eugonadal males with T2DM at baseline and after 22 weeks of treatment in those with hypogonadism.


The mRNA expression of AR, ERα (ESR1) and aromatase in adipose tissue from hypogonadal men was significantly lower as compared to eugonadal men, and it increased significantly to levels comparable to those in eugonadal patients with T2DM following testosterone treatment. AR mRNA expression was also significantly lower in MNC from hypogonadal patients compared to eugonadal T2DM patients. Testosterone administration in hypogonadal patients also restored AR mRNA and nuclear extract protein levels from MNC to that in eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are lower in men with hypogonadism. Testosterone treatment restored AR expression levels to that comparable to levels in eugonadal men.


We conclude that, contrary to our hypothesis, the expression of AR, ERα and aromatase is significantly diminished in hypogonadal men as compared to eugonadal men with type 2 diabetes. Following testosterone replacement, there is a reversal of these deficits.

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Sandeep Dhindsa, Husam Ghanim, Kelly Green, Sanaa Abuaysheh, Manav Batra, Antoine Makdissi, Ajay Chaudhuri, Sartaj Sandhu and Paresh Dandona


Insulin has anabolic effects on skeletal muscle. However, there is limited understanding of the molecular mechanisms underlying this effect in humans. We evaluated whether the skeletal muscle expression of satellite cell activator fibroblast growth factor 2 (FGF2) and muscle growth and differentiation factors are modulated acutely by insulin during euglycemic–hyperinsulinemic clamp (EHC).

Design and methods

This is a secondary investigation and analysis of samples obtained from a previously completed trial investigating the effect of testosterone replacement in males with hypogonadotropic hypogonadism and type 2 diabetes. Twenty men with type 2 diabetes underwent quadriceps muscle biopsies before and after 4 h of EHC.


The infusion of insulin during EHC raised the expression of myogenic growth factors, myogenin (by 72 ± 20%) and myogenin differentiation protein (MyoD; by 81 ± 22%). Insulin reduced the expression of muscle hypertrophy suppressor, myogenic regulatory factor 4 (MRF4) by 34 ± 14%. In addition, there was an increase in expression of FGF receptor 2, but not FGF2, following EHC. The expression of myostatin did not change.


Insulin has an acute potent effect on expression of genes that can stimulate muscle differentiation and growth.