3.1 Study subjects This was a case-control study, conducted between May 2016 and February 2017, and involving 131 adult Bahraini T2DM patients. The Research and Ethics Committee of Arabian Gulf University approved the study protocol.  See Appendix 1.

Appendix 2 illustrate the Research and Ethics Committee of King Hamad University approved the examination convention .All participants were given composed educated assent  (Study and Research Approval Form), see Appendix 3. Patients were recruited from the adult endocrinology units in Bahrain at King Hamad University Hospital.

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  Controls consisted of 81 normoglycemic subjects of both genders and were recruited either as blood bank donors or as volunteers. A unified questionnaire was filled by the investigator for the patients and controls. See Appendix 4. Then the data were entered into an EXCEL for Windows statistical package, either as text (TXT), continuous (CON), or categorical (CAT) variables.  Information collected included:• Personal data: name, age, gender, nationality and diabetes complications. • Clinical Profile: Status (patient or control; medication, diet), the age of disease onset, and disease duration and biochemical profile. To protect the identity of study participants, patients and controls were provided with a standard code number.3.

2 Inclusion and exclusion criteriaSamples were collected from (A) diabetic Bahraini patients who are under oral hypoglycemic agents with high C-peptide levels and no microvascular complications, mainly peripheral neuropathy (B) insulin-treated diabetic Bahraini patients with low C-peptide levels as illustrated in Figure 7. The patients will be selected based on serum chemistry analysis and clinical examination of T2DM males and females aged 30 and above. A diabetes diagnosis is based on clinical and laboratory features as per the American Diabetes Association guidelines (American Diabetes Association, 2012), and later revised (American Diabetes Association, 2014), which were consistent with WHO classification (Expert Committee on Diagnosis and Classification of Diabetes Mellitus, 1997).

  3.2.1 Inclusion criteriaDemographic details were collected from study subjects, which include age at presentation, gender, height (m) and weight (kg) for BMI; kg/m2 calculation, the duration of diabetes (? 4 year history of diabetes), ? 4 year history of hypertension (140/90 mmHg), family history of diabetes (including its complications), ? 300 mg/day proteinuria and diabetes management, including date of initiation and/or discontinuation of oral agents and/or insulin. Information on T2DM treatment will also be entered. 3.2.2 Exclusion criteriaPresence of vascular diseases, stroke, allergic reaction to study drug, hypertension of secondary cause.

 The criteria for the diagnosis of diabetes in non-pregnant adults are based on the Expert Committee criteria first proposed in 1997 (Expert Committee, 1997), and later modified in 2003 4. These are consistent with related diagnostic criteria of the American Diabetes Association (American Diabetes Association, 2014).1- Symptoms of DM (polyuria, polydipsia, and weight loss mainly in T1DM), plus casual plasma glucose concentration  200 mg/dl (11.1 mmol/l); casual glucose concentration defined as the concentration at any time of the day, irrespective of the time since the last meal.2- FPG concentrations  126 mg/dl ( 7.0 mmol/l); fasting indicating no caloric intake for at least 8 hours.3- 2-hour post glucose load  200 mg/dl (11.1 mmol/l) during OGTT.

The test should be performed using a glucose load (equivalent of 75 g anhydrous glucose dissolved in water).4- Impaired fasting glucose (IFG): where the FPG falls between 110 mg/dl and <126 mg/dl (6.1-7.0 mmol/L).5- Impaired glucose tolerance (IGT): where the 2-hour post glucose load is 7.

8 and less than 11.1 (200mg/dl) and the fasting if measured is less than 7 mmol/L (126 mg/dl).OGTT is not recommended for routine clinical assessment (American Diabetes Association, 2014, Genuth et al.

, 2003). T1DM patients typically present with intense side effects of diabetes and marked elevation blood sugar level, compared with T2DM patients. ADA recommended routine screening for T2DM beginning at age 45, especially with overweight individuals with known risk factors of diabetes (e.g. family history of T2DM, a personal history of gestational diabetes), and should be repeated every three years if the results are normal 112. Haemoglobin A1c (HbA1c) levels must be checked two-three times/year following the confirmed diagnosis of diabetes 113; the recommended HbA1c level is equal to or below 7% (American Diabetes Association, 2014).

Along with repeated daily blood sugar tests, HbA1c testing provides information on the long-term diabetes control and effectiveness of diabetes treatment plan 113.