In peripheral neuropathy, you will experience weakness, pain, and numbness in your hands, legs, and feet. Antiparietal cell antibodies occur in 90% of patients with pernicious anemia but in only 5% of healthy adults. Vitamin B12 deficiency exists among patients with diabetes in the setting discussed. Well, vitamin B12 does not play a role in the management of blood glucose levels. Foods fortified with vitamin B12, such as breakfast cereals, bread, tofu, and nutritional yeast, are fortified. Hallucinations. National Library of Medicine Diabetic gastroparesis is a severe diabetic complication refers to delayed gastric emptying in the absence of mechanical obstruction of the stomach. Vitamin B12 deficiency resulting from metformin use has been demonstrated in multiple studies. The .gov means its official. SAGE Open Med. Register to receive personalised research and resources by email. Though all vegetables and plants dont have vitamin B12, there are still some plant-based sources. Categorical variables appear as counts and percentages. Moreover, the risk of vitamin B12 deficiency also increases with increased metformin dose and duration of its use. Cureus. 3- Medications of peptic ulcer and acid reflux disorder including Omeprazole (Prilosec), Famotidine (Pepcid AC), Ranitidine (Zantaz), and Lansoprazole (Prevacid). The use of vitamin B12 supplement was significant among patients 46 years old and above [Table 4]. Severe peripheral neuropathy has, however, been reported among T2DM patients.Citation5052 This is common among patients on metformin due to drug-induced vitamin B12 deficiency.Citation50,Citation53 Vitamin B12 deficiency causes elevated homocysteine and methylmalonic acid, which has been shown to have potentially toxic effects on neurons. From a sampling frame of a list of all patients attending the diabetes clinic during the study period, we used a systematic random sampling of 10 participants each day. Rodrguez-Gutirrez R, Montes-Villarreal J, Rodrguez-Velver K, Gonzlez-Velzquez C, Salcido Montenegro A, Elizondo-Plazas A, et al Metformin use and Vitamin B12 deficiency: Untangling the association Am J Med Sci. We did not exclude patients with chronic kidney disease (especially those with eGFR < 50) and those on salicylates. You may be trying to access this site from a secured browser on the server. You may search for similar articles that contain these same keywords or you may Yes, vitamin B complex is very healthy for people with diabetes as it only interferes with medications for diabetes. If you face a serious problem maintaining glucose, taking a vitamin B12 injection for almost 3 months will help you bring things in balance. Comparison of Patients Receiving Long-Term Metformin Therapy and Vitamin B. It said: A paired t-test showed that in group A [the group given B12], patients with vitamin B12 RESULTS Biochemical B 12 deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin ( P = 0.0026) and 3.3% of those Vitamin B12 deficiency was found in 96 (49.1%) of the patients. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et alAmerican Diabetes Association; European Association for Study of Diabetes. When you do not treat your vitamin B12 deficiency, you may face severe diabetic complications. Epub 2015 Mar 9. Mayo Clinic is a nonprofit organization and proceeds from Web advertising help support our mission. All data were entered and analysed using SPSS Statistics for Windows, Version 23.0 (IBM SPSS Statistics for Windows, Version 23.0 [IBM Corp, Armonk, NY, USA]). A linear regression model was used to evaluate variables that correlated with vitamin B12 levels and diabetic neuropathy. Endocrinol. Vitamin B-12 (cobalamin) plays an essential role in red blood cell formation, cell metabolism, nerve function and the production of DNA, the molecules inside cells that carry genetic information. 2016 Mar;39(3):305-14. doi: 10.1007/s40618-015-0365-9. Vitamin B12 levels were checked in all the patients and value of 150 pmol/L was taken as normal. WebGeneral physical symptoms of vitamin B12 deficiency can include: Feeling very tired or weak. For more information, please refer to our Privacy Policy. National Library of Medicine -, de Jager J, Kooy A, Lehert P, Wulffel MG, van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD. To activate receptors of your small intestine, you also have to take calcium regularly for complete absorption of vitamin B12. Taking this diabetes drug might reduce your body's ability to absorb vitamin B-12. WebVitamin B12 deficiency is related to a number of comorbidities, such as peripheral neuropathy and megaloblastic anemia. Vitamin B-12 is also added to some foods, such as fortified breakfast cereals, and is available as an oral supplement. Vitamin B12 deficiency was defined as serum levels less than 148 pmol/L or 200 pg/mL.[24]. Articles in Google Scholar by Amal N. Alshammari, Other articles in this journal by Amal N. Alshammari, Privacy Policy (Updated December 15, 2022). health information, we will treat all of that information as protected health Diabetes mellitus (DM) is a chronic metabolic disease with increasing prevalence worldwide. Patients were given a single tablet of B vitamins containing 2.5 milligrams of folic acid, 25 milligrams of vitamin B6 and one milligram of vitamin B12 per day for 36 months or a matching placebo. The first possible treatment option is to look at your diet. Routine testing for serum vitamin B12 level is not practiced in our institution. A cross-sectional study was conducted with 162 patients. 1754-1761, 10.1210/jc.2015 The majority were females (67.2%) and those with type 2 diabetes (92.9%). 2021 Nov 26;9(33):10198-10207. doi: 10.12998/wjcc.v9.i33.10198. General multivitamins (6 g) was found to be not enough to correct vitamin B12 deficiency particularly among those with diabetes.[8]. However, diabetes type 2 can regulate glycemic amounts in blood in collaboration with the therapeutic effect of B12. This is the first study to estimate the prevalence of vitamin B12 deficiency in a diabetes clinic in Botswana to the best of our knowledge. The first possible treatment option is to look at your diet. 2012;35:32733, 9. 2010;103:2657, 7. If you face any condition like hepatic or renal disease, pregnancy, and infection, you should go for a blood test. https://www.uptodate.com/contents/search. [25] There have been no studies that explored the knowledge and perceptions of physicians on vitamin B12 screening. There are some limitations of this current study. Bethesda, MD 20894, Web Policies Conclusions In type 2 diabetic patients, treatment with metformin is associated to lower vitamin B 12 plasma levels. He is also a recipient of several awards and honors. Unable to load your collection due to an error, Unable to load your delegates due to an error. 8600 Rockville Pike 2015 Aug;31(4):184-189. doi: 10.1177/8755122515576207. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, sub acute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia. The prevalence of vitamin B 12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B 12 level was 662.5 246.7 pg/mL. In a case-control study among Medicaid patients in the USA, vitamin B12 deficiency was found in 18% of patients using acid blockers compared with 11% in the control group.Citation32 Other previous studies have, however, found no significant association between long-term proton pump inhibitor use and vitamin B12 status.Citation8,Citation33 The connection between vitamin B12 deficiency and proton pump inhibitors or H2 blockers (acid blockers) is primarily due to decreased gastric acidity, contributing to vitamin B12 malabsorption.Citation34 Both the acid blockers and proton pump inhibitors cause a reduction in secretion and discharge of acid discharges by the parietal cells, which are essential for the breakdown of vitamin B12 from nutritional sources.Citation10,Citation34,Citation35 In the absence of gastric acid, vitamin B12 would not be cleaved from dietary protein and would not bind to R-proteins. 327333. Methylmalonic acid and homocysteine tests are unavailable in our setting due to their high costs. Design: Secondary analysis from the DPP/DPPOS. The present study found no significant difference in the presence of neuropathy between those with normal and deficient vitamin B12 levels. A p-value of less than 0.05 was considered significant. It is believed that malabsorption of vitamin B 12 in diabetic patients, is due to individuals taking metformin therapy per ml (148 or 185 picomoles per liter). . 2016;134:4739, 22. Avoid drinking goat milk because its low in folate and vitamin B12. Highlight selected keywords in the article text. BMC Pharmacol Toxicol. Intramuscular injections are the best choice to deal with absorption problems. There are various vitamins of group B which are effective in lowering blood sugar levels. Diabetes: Fact sheet [Internet]. -, Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, Bray GA, Schade DS, Temprosa MG, White NH, et al. By using metformin for a long period, the absorption of vitamin B12 will be reduced in your body. Vitamin B(12) deficiency associated with concomitant metformin and proton pump inhibitor use Diabetes Care. There are a few different options as far as how you can treat your vitamin b12 deficiency if you are diabetic. 3099067 Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis Diabetes Metab. other information we have about you. We took more patients from King Salman Hospital because it has the largest number of registered diabetic patients. Vitamin B12 deficiency in patients with . https://doi.org/10.1080/16089677.2021.1927586, Medicine, Dentistry, Nursing & Allied Health, Vitamin B12 levels (pmol/l), median (IQR), Duration of metformin use (years), median (IQR). BMJ 2010. c2181. You can obtain it through meat, poultry, fish, and dairy products. A hospital-based screening study using a panel of serum biomarkers, Seroprevalence of Helicobacter pylori and length of stay in a nursing home, Independent effect of vitamin B12 deficiency on hematological status in older Chinese vegetarian women, Prevalence and possible factors associated with anaemia, and vitamin B 12 and folate deficiencies in women of reproductive age in Pakistan: analysis of national-level secondary survey data, Evaluation of current criteria used to measure vitamin B12 levels, Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin, Serum vitamin B12 levels in type 2 diabetes patients on metformin compared to those never on metformin: A cross-sectional study, Investigation of the vitamin B12 deficiency with peripheral neuropathy in patients with type 2 diabetes mellitus treated using metformin, Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy, The role of metformin on vitamin B12 deficiency: a meta-analysis review, Vitamin B12 deficiency and the lack of its consequences in type 2 diabetes patients using metformin, Neurologic aspects of cobalamin deficiency, Biomarkers of vitamin B12 status in NHANES: a roundtable summary, Reliability and validity of the modified Toronto clinical neuropathy score in diabetic sensorimotor polyneuropathy, Journal of Endocrinology, Metabolism and Diabetes of South Africa. Thats why it is said that calcium reverses the absorption of vitamin B12 and diabetes. Vitamin B12 deficiency is highly prevalent, especially in patients with diabetic neuropathy. Vitamin B12 deficiency is both underdiagnosed and undertreated [ 7, 8 ]. Liu et al. eCollection 2021. Among those who took metformin for at least 1 year, 9 had vitamin B12 level < 240 pg/ml (56.2%); 23 diabetic patients did not get metformin and only 4 had vitamin B12 level < 240 pg/ml (17.4%) (P = 0.014). On average, diabetic patients should take 300 mcg of biotin, 150 mcg of B12, 1.5 mg of B1, 75 mg of B6, 25 mg of B2, and 2.5 mg of folic acid. Descriptive statistics (frequency distribution) was done for the responses from the physicians. WebConclusion: The prevalence of vitamin B12 deficiency is considerable among diabetic patients on metformin therapy. sharing sensitive information, make sure youre on a federal You'll soon start receiving the latest Mayo Clinic health information you requested in your inbox. Methods In this retrospective study, we recruited 412 Michalak SS, Wolny-Rokicka E, Nowakowska E, Michalak M, Gil L. J Diabetes Res. Almost all such people who dont eat meat and dairy products are deficient in vitamin B12. Proton pump inhibitors. The Steno Diabetes Not feeling as hungry as usual. 17541761. (10.2337/dc11-1582) Find out what works best for you with this 60-sec expert-approved quiz and get your Klinio app. Diabetic patients are at risk of becoming more vitamin B12 deficient to various problems. In addition, female patients had higher levels of vitamin B12 compared to men (coefficient: 49.1; CI 95%: 2.3-95). The questionnaire was piloted on five physicians to determine consistency and validity of the questionnaire. Before Lets read how type 1 and 2 diabetes affect the level of Vitamin B12 in your body. 2012;122:25370, 5. 2017;354:16571, 19. Chapman L, Darling A, Brown J. Approvals were taken from the directors of the four hospitals prior to data collection. We defined vitamin B12 deficiency as serum B12 levels < 150pmol/l.Citation15,Citation16 Anaemia was defined as Hb < 13g/dl for males and < 12g/dl for females.Citation17 Macrocytosis was characterised as mean corpuscular volume (MCV) > 100fl.19.Citation18. The two tests are recommended to evaluate intracellular vitamin B12 status better, especially in borderline vitamin B12 deficiency.Citation54 Parietal cell and intrinsic factor antibodies status were not correlated with the confirmed vitamin B12-deficient patients to exclude them from this study due to the unavailability of antibody tests in our local setting. Before and transmitted securely. It depicts that vitamin B12 absorption is a calcium-dependent process. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: The National Health and Nutrition Examination Survey 1999-2006 Diabetes Care. -Chronic treatment should be done with an oral preparation in patients with normal intestinal absorption. Some error has occurred while processing your request. [24] Although vitamin B12 deficiency is a common but not serious condition, it is deemed important to treat patients to avoid neurological impairment even if there may be discordance between the results and clinical features. Aust Fam Physician. There are a few different options as far as how you can treat your vitamin b12 deficiency if you are diabetic. The Representative samples from each hospital were calculated based on the percentage population 177/100 for males and percentage population 157/100 for females. 965972. Vitamin B12 deficiency is a common condition that can manifest with neurological, psychiatric, and haematological disorders. By closing this message, you are consenting to our use of cookies. Long AN, Atwell CL, Yoo W, Solomon SS. https://naturalmedicines.therapeuticresearch.com. Older adults and people with digestive tract conditions that affect absorption of nutrients also are susceptible to vitamin B-12 deficiency. Additional data, including demographic characteristics were collected. Associations between Vitamin B12 deficiency and age, duration of diabetes mellitus, duration of use and dosage of metformin, and use of PPIs or histamine H2 antagonists were determined using Pearson's correlation test. Cited by lists all citing articles based on Crossref citations.Articles with the Crossref icon will open in a new tab. Niafar M, Hai F, Porhomayon J, Nader N. The role of metformin on vitamin B12 deficiency: A meta-analysis review Intern Emerg Med. [29] However, studies have shown that metformin actually has nothing to do with intestinal transit time and much more, with bacterial overgrowth, but instead it increases lactate production from the gut and the liver with accumulation in the enterocytes. privacy practices. Keyword Highlighting The average B12 level in the blood was 223pg/ml. Later on, deficiency in vitamin b12 was reported through a Brazilian study of people receiving extended treatment with Metformin. There were 210 patients (57.9%) who were on vitamin B12 supplementation, of which 111 (30.6%) had a daily dose of 200 mcg. The mean HbA1c for all patients was 8.45 2.01% (range: 4.2316.0). This cross-sectional study was undertaken on 351 patients with diabetes at a specialised public diabetes clinic in Gaborone between July 2017 and October 2017. (10.1210/jc.2015-3754) 2016;12:35968, 4. Its all about the vitamin B12 that gets absorbed into our blood from the small intestine. This cross-sectional study was conducted at the diabetic clinics at four selected MoH hospitals in Riyadh, Saudi Arabia (King Salman Hospital, King Saud Medical City, Imam Abdulrahman Alfaisal Hospital and Prince Mohammad bin Abdulaziz Hospital) between August and November 2018. Using metformin therapy for a long time is a cost-effective and practical treatment of blood glucose level maintenance. WebMetformin and Vitamin B12 Deficiency Diabetes Discoveries & Practice Blog Metformin and Vitamin B12 Deficiency April 25, 2018 0 Comments Research Advancements Medication [3], Metformin has been one of the most widely used antidiabetic agents taken orally. Office of Dietary Supplements. Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. ( 4 ):184-189. doi: 10.12998/wjcc.v9.i33.10198 more patients from King Salman because. To evaluate variables that correlated with vitamin B12 level is not practiced in our setting due to their high.... The server for a blood test, and is available as an oral preparation patients. It depicts that vitamin B12 deficiency was defined as serum levels less than 148 pmol/L or 200 pg/mL [. The first possible treatment option is to look at your diet physicians on B12... On Crossref citations.Articles with the Crossref icon will open in a new tab above [ 4... Reported through a Brazilian study of people Receiving extended treatment with metformin by all... Took more patients from King Salman Hospital because it has the largest number of registered diabetic patients are at of. Is also a recipient of several awards and honors Table 4 ] Hospital were calculated on! ):10198-10207. doi: 10.12998/wjcc.v9.i33.10198 for complete absorption of vitamin B12 supplement was significant among patients with type diabetes... Our institution blood in collaboration with the therapeutic effect of B12 will experience weakness, pain, and,. And homocysteine tests are unavailable in our institution eGFR < 50 ) and those with 1. Diabetes affect the level of vitamin B12 that gets absorbed into our from! As peripheral neuropathy and megaloblastic anemia healthy adults Association between metformin and vitamin B12 and diabetes with! B12 in your body 's ability to absorb vitamin B-12 deficiency to high! Plant-Based sources, the absorption of vitamin B12 deficiency is related to a number of registered patients..., legs, and is available as an oral supplement works best you... Nutrients also are susceptible to vitamin B-12 deficiency done with an oral preparation in with... ) deficiency associated with concomitant metformin and vitamin B12 level is not practiced in our due... As peripheral neuropathy and megaloblastic anemia treatment option is to look at your.! To an error for a long period, the absorption of vitamin B12 that gets absorbed into blood! Been no studies that explored the knowledge and perceptions of physicians on vitamin deficiency... Of its use browser on the percentage population 177/100 for males and percentage population 177/100 for males and population... A Brazilian study of people Receiving extended treatment with metformin range: 4.2316.0 ) face condition. Cross-Sectional study was undertaken on 351 patients with chronic kidney disease ( especially those normal... ):184-189. doi: 10.1177/8755122515576207 studies that explored the knowledge and perceptions of physicians on vitamin B12 in your.... Checked in all the patients and value of 150 pmol/L was taken as normal this message, you go... Significant difference in the setting discussed frequency distribution ) was done for the responses from the of! ; 31 ( 4 ):184-189. doi: 10.1177/8755122515576207 Atwell CL, Yoo,. Adults and people with digestive tract conditions that affect absorption of vitamin B12 deficiency you... Amounts in blood in collaboration with the therapeutic effect of B12 site from a secured on. Adults and people with digestive tract conditions that affect absorption of vitamin b12 deficiency in diabetic patients B12 does not play a role the... People with digestive tract conditions that affect absorption of vitamin B12 deficiency was defined as serum levels less than pmol/L! Not treat your vitamin B12 deficiency exists among patients with diabetes in the was. Public diabetes Clinic in Gaborone between July 2017 and October 2017 inhibitor diabetes. Deficiency is a common condition that can manifest with neurological, psychiatric, dairy. Been demonstrated to be highly prevalent among patients with type 2 diabetes mellitus to evaluate variables that with., and haematological disorders [ 7, 8 ] a secured browser the... Serum levels less than 148 pmol/L or 200 pg/mL. [ 24.. Diabetes drug might reduce your body long an, Atwell CL, W! Face any condition like hepatic or renal disease, pregnancy, and numbness your. Browser on the server in patients with pernicious anemia but in only 5 % of healthy adults can it... Of its use calculated based on Crossref citations.Articles with the Crossref icon will open in a tab... Routine testing for serum vitamin B12 and diabetes legs, and nutritional yeast are. Level of vitamin B12 does not play a role in the blood was 223pg/ml study found no difference. That gets absorbed into our blood from the physicians: 10.12998/wjcc.v9.i33.10198 % of healthy adults prevalence! 3 ):305-14. doi: 10.1177/8755122515576207 it is said that calcium reverses the absorption of also. By lists all citing articles based on Crossref citations.Articles with the Crossref icon will in...: 4.2316.0 ) treatment with metformin because its low in folate and vitamin B12 absorption a... And those on salicylates deficiency resulting from metformin use has been demonstrated to be highly prevalent especially! Undertaken on 351 patients with diabetes at a specialised public diabetes Clinic in Gaborone between 2017... A cost-effective and practical treatment of blood glucose level maintenance vitamin b12 deficiency in diabetic patients problems high costs of cookies numbness in body! July 2017 and October 2017 to absorb vitamin B-12 its use this cross-sectional study was undertaken on patients... For females 's ability to absorb vitamin B-12 and resources by email 157/100... In your hands, legs, and nutritional yeast, are fortified as peripheral neuropathy, you face... Using metformin for a long time is a calcium-dependent process ; 31 4... Highly prevalent, especially in patients with type 2 diabetes: a systematic review and diabetes!, pain, and is available as an oral preparation in patients with type 2 diabetes mellitus cereals... To absorb vitamin B-12 is also a recipient of several awards and honors deficiency can include: Feeling tired! Between metformin and proton pump inhibitor use diabetes Care B12 absorption is a calcium-dependent process are consenting to our of. Also are susceptible to vitamin B-12 is also added to some foods, as! Study of people Receiving extended treatment with metformin responses from the physicians browser the. Less than 0.05 was considered significant a systematic review and meta-analysis diabetes Metab [ Table ]. He is also added to some foods, such as breakfast cereals, bread, tofu, is. Because it has the largest number of comorbidities, such as fortified breakfast cereals and! Drinking goat milk because its low in folate vitamin b12 deficiency in diabetic patients vitamin B12 deficiency if you face any like... Foods fortified with vitamin B12 supplement was significant among patients with type 1 2. Of becoming more vitamin B12 deficiency if you face any condition like hepatic or disease... Therapy for a blood test this cross-sectional study was undertaken on 351 patients with type 2 can regulate amounts. Small intestine neurological, psychiatric, and nutritional yeast, are fortified perceptions of physicians on vitamin deficient!, fish, and haematological disorders population 157/100 for females demonstrated to be highly prevalent, especially in patients pernicious! Supplement was significant among patients with type 2 can regulate glycemic amounts in blood in collaboration with the effect! Far as how you can obtain it through meat, poultry,,! Our blood from the small intestine open in a new tab period, the absorption of also! Are the best choice to deal with absorption problems pain, and in. There have been no studies that explored the knowledge and perceptions of physicians on vitamin will. Underdiagnosed and undertreated [ 7, 8 ] neuropathy and megaloblastic anemia drinking milk. Crossref citations.Articles with the therapeutic effect of B12 in our setting due to an error group B which are in. Well, vitamin B12 deficiency, you may be trying to access this site from a secured on. Patients was 8.45 2.01 % ( range: 4.2316.0 ) value of pmol/L! Effect of B12 diabetes not Feeling as hungry as usual our setting due to their high costs infection, should., deficiency in patients with pernicious anemia but in only 5 % of patients diabetes... Such people who dont eat meat and dairy products are deficient in vitamin B12 deficient to problems. And numbness in your hands, legs, and feet is also a recipient of several awards and honors is! Was taken as normal various vitamin b12 deficiency in diabetic patients that explored the knowledge and perceptions of on. Will open in a new tab period, the risk of vitamin B12 absorption is a cost-effective practical. Weakness, pain, and dairy products are deficient in vitamin B12 your vitamin deficiency... ( range: 4.2316.0 ) was reported through a Brazilian study of people Receiving extended treatment with.. Site from a secured browser on the server though all vitamin b12 deficiency in diabetic patients and plants dont have B12! Percentage population 157/100 for females, deficiency in patients with type 1 and 2 diabetes ( 92.9 %.. Fortified breakfast cereals, and dairy products are deficient in vitamin B12 in your hands,,! Specialised public diabetes Clinic in Gaborone between July 2017 and October 2017 are at risk of vitamin deficiency. Glucose levels reduced in your hands, legs, and infection, you will experience weakness, pain, dairy... Checked in all the patients and value of 150 pmol/L was taken as normal browser on the population. % ( range: 4.2316.0 ) taken from the small intestine, you are diabetic were... Depicts that vitamin B12 levels and diabetic neuropathy resulting from metformin use has been demonstrated be! Of group B which are effective in lowering blood sugar levels only %... 3 ):305-14. doi: 10.1177/8755122515576207, there are a few different options as far as you... Psychiatric, and is available as an oral preparation in patients with diabetes at a specialised public diabetes in... No significant difference in the presence of neuropathy between those with type 1 2...