Metformin Usage Index and Vitamin B12 Status in Egyptian Type 2 Diabetic Patients

Diabetes Mellitus Clinical Trial

Official title:

Metformin Usage Index and Vitamin B12 Status in Egyptian Type 2 Diabetic Patients : A Case Control Study .

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04882332
• Other study ID #: N-25-2021
• Status: Recruiting
• Start date: May 5, 2021
• Est. completion date: October 2022

Study information

• Verified date: March 2022
• Source: Cairo University
• Contact: Nehal H Elsaid
• Phone: 01004389020
• Email: nihalhamdyelsaid[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Current data estimated that 451 million people, (age 18-99 years) suffered from diabetes world wide in 2017, and are expected to rise to 693 million by 2045. Among them, type 2 diabetes mellitus (T2DM) accounts for around 90% of all cases with diabetes.

T2DM is associated with several deterimental microvascular and macrovascular complications (Annani-Akollor ME et al ., 2019) . As such, effective management of the disease is crucial.

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend metformin as the first therapeutic choice for T2DM management with concurrent lifestyle modifications. Reports indicated that metformin improves peripheral insulin sensitivity and reduces the risk of cardiovascular mortality in T2DM in addition to its beneficial effects on weight loss and vascular protection.

Nonetheless, as with most medications, metformin has some side effects. Though most of these side effects are mild, reports indicated that metformin use is associated with diminution of vitamin B12 level . Also, advanced age of patients with T2DM, nutritional deficiency, and malabsorption are other contributing factors for its deficiency .

The proposed mechanisms for deficiency include, impairment of calcium dependent absorption from the gut, alteration in small bowel motility resulting in bacterial overgrowth, and a reduction in intrinsic factor levels .

Metformin-induced vitamin B12 deficiency has also been associated with neuropathy. The neuropathy associated with vitamin B12 deficiency ranges from paresthesia and attenuated peripheral sensation in response to changes in mental status and proprioception which overlap with diabetic neuropathy.

The progression of vitamin B12 deficiency-induced neurologic damage can, however, be abated through early detection and vitamin B12 therapy. Nonetheless, if peripheral neuropathy due to deficiency of vitamin B12 is misconstrued as diabetic peripheral neuropathy , permanent neurological damage may occur.

Several studies have investigated the individual effects of the dose and duration of metformin therapy on vitamin B12 levels .The reported results are inconsistent, with some studies reporting an association with the dose but not the duration and other studies reporting an association only for the duration. however, A few studies did not find an association with either the dose or the duration..

This could be attributed to the fact that, in any given patient with T2DM, vitamin B12 levels could be influenced predominantly by either the dose or the duration of metformin therapy. Hence, it is important to involve both the dose and duration of metformin therapy into the assessment of vitamin B12 deficiency.

Micronutrient deficiencies constitute a global health issue, particularly among countries in the Middle East .The World Health Organization (WHO) has divided this region into overlapping country clusters with regard to nutrition stages and dominant nutrition problems, including major risk factors and underlying causes, program interventions, and gaps in response to these problems.

Countries in early nutrition transition (e.g., Egypt, Jordan, Lebanon, Morocco, and Palestine) are typically characterized by a moderate prevalence of overweight and obesity, moderate levels of undernutrition in specific population groups, and widespread micronutrient deficiencies/inadequacies.

Metformin Usage Index is the product of the dose of metformin (mg) used and its duration divided by 1000. An index which incorporates both of these factors would not only be useful to understand the cumulative impact on vitamin B12 levels but also provide an objective threshold for initiating vitamin B12 supplementation .

So , the aim of this study is to assess the relationship between the dose and duration of metformin therapy with vitamin B12 levels using the "Metformin Usage Index" (MUI) in Egyptian type 2 diabetic patients where the incidence of nutritional deficiencies are not uncommom in order to formulate their appropriate management strategies .

The aim of our study is to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in Egyptian patients with type 2 diabetes mellitus (T2D).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: October 2022
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• Men and women aged 20 to 65 years old with controlled and uncontrolled type 2 DM

Exclusion Criteria:

• T2DM patients who are pregnant/lactating women,

• newly diagnosed with T2DM (< 3 months),

• who receive vitamin B12 supplementation or proton-pump inhibitors over the last 6 months,

• alcoholics ,

• known cases of malabsorption (gastrointestinal surgery, inflammatory bowel diseases and gluten allergy),

• chronic kidney disease,

• pernicious anemia

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

Other:
• sampling for diabetes control parameters
Intravenous blood withdrawal for a sample of fasting blood glucose (FBG), 2 hr postprandial blood glucose (2 hr -PPG), fasting lipids {total cholesterol (TC), triglycerides (TAG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)}, glycosylated hemoglobin (Hb A1c) ,fasting insulin level and Vitamin B 12 levels
• Sampling for vitamin B12 level
Intravenous blood sampling for a sample of vitamin B12 level

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo	Manial

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

References & Publications (1)

Ahmed MA, Muntingh G, Rheeder P (2016) Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol 17(1):44. https ://doi.org/10.1186/s4036 0-016-0088-3. Alvarez M, Sierra OR, Saavedra G, Moreno S (2019) Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study. Endocr Connect 8(10):1324- 1329. https ://doi.org/10.1530/EC-19-0382. Annani-Akollor ME, Addai-Mensah O, Fondjo LA, et al.(2019) Predominant complications of type 2 diabetes in kumasi: a 4-year retrospective cross-sectional study at a teaching hospital in Ghana. Medicina (B Aires). 2019;55(5): 125.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between Metformin Usage Index and Vitamin B12 status among Egyptian patients with type 2 diabetes	The relationship between MUI and vitamin B12 levels will be assessed among the studied groups	6 months