Diabetes mellitus is a metabolic syndrome, prevalence of which is increasing day by day worldwide. The disease is related to a number of micro vascular and macro vascular changes mainly due to hyperglycemia which accelerates the mechanism of deposition of advanced glycation end product in the capillary network leading to hypoxic changes in the tissues resulting in end organ diseases. Diabetic micro vascular complications leads to blindness, end stage renal disease and limb amputations. Top priority treatment of diabetes remains insulin replacement therapy which is till date administered only by parenteral route, which is associated with decreased compliance due to fear of injection and hindrance in daily routine of life. To solve this problem, a number of routes of administrations to name a few nasal, oral and transdermal routes are investigated for long term insulin therapy. Till date no drug has come to the market in its final form. Present study was conducted in three phases that is a survey, study of emulgel in large animal model and in human subjects. Prevalence of diabetic complications in low income group presented in diabetes OPD of Sind Government Hospital, New Karachi Township: Aim of the present survey was to study the prevalence of diabetic micro vascular complications in the low income population group of New Karachi Township. Additionally, what is the impact of metabolic syndrome in the prevalence of complications? To serve the purpose a sample size of one hundred and fifty four participants with type II diabetes for more than 5 years was collected at 80% power and 10% prevalence of diabetes in Pakistan. After acquiring consent from the participants, they were interviewed in detail about their disease, general condition, systemic review, history of co-morbidities, duration of diabetes and medication history. Detailed checkup of feet and eyes by trained personals was carried out followed by blood and urine sample collection for laboratory investigations which included glucose, lipid and kidney profiles. Many parameters were also calculated using different formulas from the data collected by these laboratory investigations. Statistical analysis was carried out by using SPSS -20 (IBM) with Pearson‟s chi squared test for correlation between categorical variables, student‟s t-test for numerical data with level of significance at p < 0.05. Response rate was 50%, and average age of the participants was 50 years. 27% were men and 73% of the participants were women. 84% of the sample belonged to Urdu speaking ethnic group. 68% participants were uneducated or had primary education. Average BMI was 26.28 and average duration of diabetes was 11 years. Majority of patients were found on oral hypoglycemic agents i.e. only 28% participants were prescribed insulin out of which 20% were having insulin along with oral hypoglycemic agents. Most important findings were that 42.89% participants presented with either type of diabetic retinopathy. Proliferative diabetic retinopathy which leads to advanced eye disease however was found 3% (n = 5). 61.69% participants presented with impaired urinary albumin creatinine ratio. 3% (n = 5) of whom presented with overt nephropathy. On the basis of Ipswich touch test, neuropathy was classified in 62% (n = 96) participants, who showed positive loss of sensations on distal phalanges. Metabolic syndrome was found in 60% (n = 93) participants. Analysis of different risk classifications revealed that 8% (n = 13) participants were at high risk to develop diabetic foot (χ2 = 92, p < 0.001),additionally 3 participant presented with active foot. 8% (n = 12) showed high risk to develop coronary artery disease in next 10 years (χ2 = 235, p < 0.001). Risk of stroke was luckily found only 1% (n = 2) in next 10 years. Risk to develop diabetic kidney disease was seen in 8% (n = 13) participants. Gender based stratification showed that average age of female participants was younger (48.5 years) than the male participants (56 years, t = 4.5, p < 0.001). Average BMI of the females (26.99) was greater than the male (24.4) participants (t = 2.88, p < 0.001). There was no gender difference found in the prevalence of microvascular complications i.e. retinopathy, nephropathy and neuropathy. However significant gender difference was found in prevalence of metabolic syndrome as 68% female and 42% male participants presented with the syndrome (χ2 = 9.57, p < 0.025). Significant coronary artery disease risk between gender strata was observed as 64% of male participants had moderate to very high risk to develop coronary artery disease in next ten years compared to females (χ2 = 46.92, p < 0.001). However, risk to develop diabetic foot and diabetic kidney disease was not found statistically different between gender groups. On the basis of metabolic syndrome strata, participants with metabolic syndrome presented with nausea vomiting (χ2 = 6.87, p < 0.001), heavy headedness (χ2 = 13.11, p < 0.001), vertigo (χ2 = 13.4, p < 0.001) and burning sensations of extremities (χ2 = 5.82, p < 0.001). All the microvascular complications were found more prevalent in metabolic syndrome strata i.e. 45% retinopathy, 76% nephropathy and 52% neuropathy. Logistic regression analysis for the complications revealed that body mass index, systolic blood pressure, cholesterol, triglycerides and nephropathy were positive correlates for presence of metabolic syndrome. Retinopathy was found affected by BMI and presence of nephropathy. Glycated hemoglobin, metabolic syndrome and urinary albumin creatinine ratio was found to positively correlate with diabetic nephropathy. Diabetic neuropathy on the other hand was found to be positively correlated with BMI, systolic BP, cholesterol, triglycerides, LDL, HDL, CHR, Serum creatinine, diabetic nephropathy and metabolic syndrome. To conclude, diabetic nephropathy and metabolic syndrome exert their influence in the development and progression of diabetic retinopathy and neuropathy. Study population is at high risk to develop diabetes and its compliations. Hypoglycemic activity of Transdermal dosage form of Insulin in large animal model Aim of this study was to evaluate the effects of optimized insulin emulgel preparation in large animals. Six sheep (Ovis aries) of either sex weighing 20 – 25 kg were used in the study. Baseline sugar level was tested and then anesthesia and hyperglycemia was induced by Ketamine (10 mg/kg) and Xylazine (0.2 mg/kg) for acute and sustained hyperglycemia. Animals were divided into two groups of three animals each. One group received subcutaneous insulin and other received emulgel with the help of a derma roller on shaved skin. The results were found comparable with the insulin injection. Emulgel followed the same pattern of hypoglycemia but a significant difference was observed between the two treatment groups at the end of the study. Hypoglycemic effect of insulin with the help of derma roller was confirmed. Effect of Transdermal insulin on human subjects Objective of this segment of study was to observe the effect of insulin emulgel on human volunteers. 32 human subjects were recruited for the study after sample size calculation at 80% power and 10% prevalence of diabetes in Pakistan. The subjects were divided into healthy and hyperglycemic volunteers. Each group consisted of 16 individuals. After written and informed consent a two day study was conducted. On day 1, baseline data was obtained. Breakfast was provided to the participants to avoid food related bias. On 2nd day participants were applied with emulgel with the help of derma roller then data of blood glucose for next 2.30 hours was collected. In healthy (normoglycemic) subjects good glycemic control was observed, as nonsignificant difference between baseline and post administration data was found. However in hyperglycemic individuals this condition was not found and emulgel was not able to control glucose level after 30 minutes resulting in exaggerated glucose curve.