Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus

Weisberg, Lawrence S.

doi:10.2215/cjn.10871014

Cited by 21 publications

(17 citation statements)

References 60 publications

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“…In this respect, Mandel et al [ 67 ] found that adjusting primary results according to animal-derived protein and potassium intake resulted in no attenuation in the association between plasma bicarbonate and diabetes, suggesting that these underlying mechanisms may be independent of dietary acid load. Furthermore, available evidence does not allow for inference on the relationship cause and effect: metabolic disturbances such as diabetes itself can affect pH status and the production of acid species [ 74 , 75 ] by affecting metabolic reactions and kidney functionality [ 76 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

2018

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Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

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Section: Discussionmentioning

confidence: 99%

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

2018

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“…Metformin is continuously detected in fake slimming formulations [57], because unlike sulfonylureas, it does not cause hypoglycaemia nor hyperinsulinemia even when administered alone in healthy subjects or patients with type 2 diabetes [58]. In some instances, however, metformin, like its withdrawn structural analogues buformin and phenformin, is known to cause lactic acidosis as a result of the very minimal liver uptake of serum lactate which is a required substrate of gluconeogenesis [59,60].…”

Section: Metforminmentioning

confidence: 99%

Counterfeit formulations: analytical perspective on anorectics

2021

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Purpose This paper examines the scope of anorectics in counterfeit weight-reducing formulations and provides insight into the present state of research in determining such adulterants. Analytical techniques utilised in profiling adulterants found in slimming products, including limitations and mitigation steps of these conventional methods are also discussed. The current legal status of the anorectics and analogues routinely encountered in non-prescription slimming formulations is also explored. Methods All reviewed literature was extracted from Scopus, Web of Science, PubMed, and Google Scholar databases using relevant search terms, such as, ‘counterfeit drugs’, ‘weight loss drugs’, ‘weight-reducing drugs’, ‘slimming drugs’, ‘anorectic agents’, and ‘counterfeit anorexics’. Legislation related to anorectics was obtained from the portals of various government and international agencies. Results Anorectics frequently profiled in counterfeit slimming formulations are mostly amphetamine derivatives or its analogues. Five routinely reported pharmacological classes of adulterants, namely anxiolytics, diuretics, antidepressants, laxatives, and stimulants, are mainly utilised as coadjuvants in fake weigh-reducing formulations to increase bioavailability or to minimise anticipated side effects. Liquid and gas chromatography coupled with mass spectrometric detectors are predominantly used techniques for anorectic analysis due to the possibility of obtaining detailed information of adulterants. However, interference from the complex sample matrices of these fake products limits the accuracy of these methods and requires robust sample preparation methods for enhanced sensitivity and selectivity. The most common anorectics found in counterfeit slimming medicines are either completely banned or available by prescription only, in many countries. Conclusions Slimming formulations doped with anorectic cocktails to boost their weight-reducing efficacy are not uncommon. Liquid chromatography combined with mass spectrometry remains the gold standard for counterfeit drug analysis, and requires improved preconcentration methods for rapid and quantitative identification of specific chemical constituents. Extensive method development and validation, targeted at refining existing techniques while developing new ones, is expected to improve the analytical profiling of counterfeit anorectics significantly.

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“…In addition, even CKD patients with minimal renal impairment but the presence of microalbuminuria or proteinuria can easily develop acute kidney injury (AKI) independent of the natural progression and/or severity of their underlying renal insufficiency (16,17). Metformin-associated lactic acidosis is rare but not nonexistent, highlighted by a recent case record in the New England Journal of Medicine (5) as well as other case reports (7,18,19), including a 2010 case series (20). The case series compared metformin-associated acidosis with other types of lactic acidosis, such as postcardiac arrest, septic shock, cardiogenic shock, mesenteric ischemia, and hemorrhagic shock, none of which had a blood pH below 7.0 except for metformin-associated acidosis (20).…”

Section: Is Metformin-associated Lactic Acidosis Real?mentioning

confidence: 99%

Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? No, We Should Never Again Compromise Safety!

Kalantar-Zadeh

Kövesdy

2016

Diabetes Care

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Metformin is and has been considered as first-line therapy for type 2 diabetes for over a quarter of a century. Like other biguanides, metformin can cause a lactic acidosis that is exceptionally rare but fatal. The likelihood of metformin-associated lactic acidosis is substantially higher in patients with kidney impairment and also among those with seemingly normal kidney function who are at risk of acute kidney injury (AKI). Hence, regulatory agencies in many industrialized nations have maintained strict renal restrictions surrounding metformin. However, there have been millions of people exposed to metformin for many years, many of them with serum creatinine values at or close to 1.5 mg/dL with estimated glomerular filtration rates (eGFRs) much below 60 mL/min/1.73 m2 who have not developed lactic acidosis. Thus, there clearly remains controversy in this area, and there has been heightened pressure to remove the renal restrictions of metformin. To provide a discussion on the pros and cons of relaxing the renal restrictions for metformin use, we provide a Point-Counterpoint. In the point narrative below, Drs. Kalantar-Zadeh and Kovesdy provide their argument that although there is little evidence of the potential benefits of metformin in kidney disease, just considering the sheer numbers of metformin users and the high fatality rate of its associated lactic acidosis, the most appropriate practice is to avoid metformin use in people with eGFR <45 mL/min/1.73 m2 or in those who are at high risk of AKI irrespective of underlying eGFR. In the following counterpoint narrative, Drs. Bakris and Molitch argue that the data from a very large analysis demonstrate clearly that serum creatinine should be supplanted with eGFR as the criteria for metformin use and that the incidence of lactic acidosis is only elevated in those with a reduced eGFR who become dehydrated for various reasons or in those exposed to some toxin resulting in AKI. Otherwise the data clearly support the use of metformin under normal circumstances down to eGFR >30 mL/min/1.73 m2.—William T. CefaluEditor in Chief, Diabetes Care

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Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus

Cited by 21 publications

References 60 publications

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

Counterfeit formulations: analytical perspective on anorectics

Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? No, We Should Never Again Compromise Safety!

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