Metformin at the Cellular Level and Dosing for Diabetes Mellitus (DM)

Pediatric Inclusion Criteria:

• Children 10-17 years.
• Both genders (male and female)
• All children must have a Primary Care Physician and/or an Endocrinologist who must be aware that the child under their care will be part of the study.
• All children must have a Primary Care Physician and/or an Endocrinologist who is considering initiating metformin therapy now or in the near future as part of standard clinical care.
• Naïve to metformin.
• Either: Prediabetic children Or diabetic children under good glycemic control

Pediatric Exclusion Criteria:

• Children ages 10-17 who do not have parental consent and/or do not give assent
• Children living in foster care
• Children with allergies to foods in the breakfast menu
• Children who currently consume any alcohol
• Children on current antidiabetic medication or those who have been on any antidiabetic medication in the 3 months prior to enrolment
• Children with a history of /or concurrent chronic disease (eg. heart, kidney, liver disease or any type of malignancy or pre-malignant condition) that required hospitalization within the last 6 months
• Pregnancy
• Refusal by a female participant who is of child bearing potential and sexually active to use contraceptive methods such as oral contraceptive pills, barrier methods and abstinence
• Children weighing less than 36 kg
• Children with any condition that increases the risk of lactic acidosis (e.g. cancer, infection, congestive heart failure, renal disease )
• Children with history of recent hospitalization for surgery, dehydration, sepsis, hypoxemia (within the past 6 months)
• Children with history of weight loss, polyuria and polydipsia
• Children who are currently enrolled in a weight management program
• Children with known hypersensitivity to metformin
• Children with a fasting blood glucose of >180mg/dl
• Children with a HbA1c level of ≥7%
• Children with glycosuria
• Children with clinical or laboratory evidence of hepatic disease- transaminase levels three times the upper normal range (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) and/or a increased level of Gamma-glutamyltransferase (GGT), Prothrombin Time (PT), International Normalized Ratio (INR) from the reference normal range and a serum albumin less than the reference normal range of the Johns Hopkins Clinical Laboratories.
• If iodinated contrast is used on a participant, due to possible acute alteration of renal function resulting in increased risk of lactic acidosis, the participant will be excluded.
• Children with renal impairment
• In children >50kg, renal impairment is defined by a serum creatinine 1.4 mg/dl or higher in females or 1.5mg/dl or higher in males OR estimated Glomerular Filtration Rates (eGFR) ≤60mL/min by the Schwartz formula.
• In children <50kg, renal impairment is defined by eGFR <100 mL/min by the Schwartz formula.
• Children with acid-base disturbance as defined by serum bicarbonate levels less than 20mEq/L or greater than 29mEq/L.

Adult Inclusion Criteria:

• Adults 18-79 years
• Both genders (male and female)
• All participants must have a Primary Care Physician and/or an Endocrinologist who must be aware that the adult under their care will be part of the study
• All participants must have a Primary Care Physician and/or an Endocrinologist who is considering initiating metformin therapy now or in the near future as part of standard clinical care.
• Naive to metformin
• EITHER: Prediabetic adults OR diabetic adults, under fair glycemic control:

Adult Exclusion Criteria:

• Pregnancy
• Adults who are not able to understand the Informed Consent document and who are unwilling to do the study
• Adults with allergies to any of the foods in the breakfast menu
• Adults on current antidiabetic medication or on any antidiabetic medication in the 3 months prior to enrolment.
• Adults with a history of /or concurrent chronic disease (e.g. heart, kidney, liver disease or any type of malignancy or pre-malignant condition) that required hospitalization within the last 6 months
• Refusal by a female participant who is of child bearing potential and sexually active to use contraceptive methods such as oral contraceptive pills, barrier methods and abstinence
• Adults with excessive current intake of alcohol (>2 drinks/day for males and >1 drink/day for females)
• Adults who have engaged in binge drinking (>5 drinks within a 2 hour period) in the last 3 months
• Adults with history of recent hospitalization for surgery, dehydration, sepsis, hypoxemia (past 6 months)
• Hypersensitivity to metformin.
• Adults with fasting blood glucose of >180mg/dl.
• Adults with HbA1c level of ≥8%
• Adults with glycosuria.
• Adults with any condition that increases the risk of lactic acidosis (e.g. cancer, infection, congestive heart failure, renal disease )
• Adults with clinical or laboratory evidence of hepatic disease- transaminase levels three times the upper normal range (AST and ALT) and/or a increased level of GGT, PT, INR from the reference normal range and a serum albumin less than the reference normal range of the Johns Hopkins Clinical Laboratories.
• If iodinated contrast is used on a participant, due to possible acute alteration of renal function resulting in increased risk of lactic acidosis, the adult participant will be excluded.
• Adults with renal impairment as defined by a serum creatinine 1.4 mg/dl or higher in females or 1.5mg/dl or higher in males OR estimated Glomerular Filtration Rates (eGFR) ≤60mL/min by Modification of Diet in Renal Disease (MDRD) formula.
• Adults with acid-base disturbance as defined as serum bicarbonate levels less than 20mEq/L or greater than 29mEq/L.

Adult Obese Control Inclusion Criteria:

• Age 18-79
• Both genders (male and female)
• BMI > 30 kg/m2

Adult Obese Control Exclusion Criteria:

• Subjects previously or currently on any diabetes medication, including metformin, will be excluded.
• Pregnancy
• Subjects with history of or concurrent chronic disease (e.g. heart, kidney, liver disease or any type of malignancy or pre-malignant condition) that required hospitalization within the last 6 months will be excluded.
• Adults with allergies to any of the foods in the breakfast menu
• Adults with excessive current intake of alcohol (>2 drinks/day for males and >1 drink/day for females)
• Adults who have engaged in binge drinking (>5 drinks within a 2 hour period) in the last 3 months