Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.

Miles, John M.; Haymond, Morey W.; Nissen, Steven; Gerich, John E.

doi:10.1172/jci110911

Cited by 106 publications

(71 citation statements)

References 37 publications

(62 reference statements)

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“…The M value, clamp glucose oxidation, and clamp glucose storage were negatively correlated with obesity expressed as percent body fat (fat mass/total weight) or body mass index (BMI) (27,42,43), and liver ketogenesis (44). In discussing that energy balance is confined to much narrower limits than metabolism of FFAs it should be noted that FFA metabis the oxidation of carbohydrate or lipid.…”

Section: Methodsmentioning

confidence: 99%

Relationship between insulin-mediated glucose disposal and lipid metabolism in man.

Lillioja¹,

Bogardus²,

Mott³

et al. 1985

J. Clin. Invest.

153

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IntroductionTo assess the possible effects of lipid metabolism on insulinmediated glucose disposal, 18 nondiabetic Pima Indian women (age 18-35 yr) were studied using 1-'4C-palmitate infusion to measure free fatty acid turnover rate followed by a euglycemic clamp (clamp) to measure in vivo insulin-mediated glucose disposal (M). Indirect calorimetry was performed in the basal state and during the clamp. This was used to assess glucose oxidation rate, lipid oxidation rate, and to calculate nonoxidative glucose disposal (storage). Basal and clamp lipid oxidation rate correlated with basal plasma free fatty acid concentration (r = 0.81, P < 0.0001, r = 0.67, P < 0.003, respectively). The fall in lipid oxidation was highly correlated with the increase in glucose oxidation during the insulin infusion (r = 0.96, P < 0.0001). The clamp lipid oxidation rate negatively correlated with the glucose oxidation rate (r = -0.85, P . 0.0001) and with the M value (r = -0.60, P < 0.01) but was not correlated with the clamp glucose storage (r = -0.2, P = 0.4). On the other hand, glucose storage appeared to make a greater contribution to the difference in M value between the upper and lower extremes of M than did glucose oxidation, as evidenced by an increase in glucose storage of 0.59 mg/kg fat-free mass times minute per 1 mg/kg fat-free mass times minute increase in glucose disposal. The M value was negatively correlated with obesity as measured by percent body fat (r = -0.64, P < 0.004), but neither basal free fatty acid concentration, basal free fatty acid turnover, basal lipid oxidation, nor clamp lipid oxidation correlated with percent body fat. We conclude that an interaction of lipid and glucose metabolism in a glucose fatty acid cycle, as proposed by Randle et al. (1), may be operative in the regulation of glucose oxidation in man. The disposal of glucose however has two components. The storage component does not appear to be associated with lipid oxidation in the way that the oxidative component is and may be regulated by a different mechanism. Since the results show that the glucose storage component plays a significant role in distinguishing between those with low and high M values, we suggest that the glucose fatty acid cycle can, at best, only partially explain impaired in vivo insulin-mediated glucose disposal. Furthermore, the data suggest that the impact of obesity on in vivo insulin resistance appears to be mediated by factors other than changes in lipid availability or metabolism.

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Section: Methodsmentioning

confidence: 99%

Relationship between insulin-mediated glucose disposal and lipid metabolism in man.

Lillioja¹,

Bogardus²,

Mott³

et al. 1985

J. Clin. Invest.

153

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“…To our knowledge, rates of ketogenesis have not been measured in hyperosmolar nonketotic patients using either organ balance or isotopic methods. Subsequent work using tracer methods (41,74) has demonstrated that even brief withdrawal of insulin from type 1 diabetic patients results in prompt development of ketosis. Insulin withdrawal from diabetic patients, however, leads to complex changes in circulating concentrations of many stress hormones.…”

Section: Lipid and Ketone Metabolismmentioning

confidence: 99%

Management of Hyperglycemic Crises in Patients With Diabetes

et al. 2001

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Abbreviations: AaO 2 , alveolar-to-arteriolar oxygen; AKA, alcoholic ketoacidosis; ARDS, adult respiratory distress syndrome; BUN, blood urea nitrogen; CPT, carnitine palmitoyl-transferase; CSF, cerebrospinal fluid; DKA, diabetic ketoacidosis; FFA, free fatty acid; HHS, hyperosmolar hyperglycemic state; IRI, immunoreactive insulin; PaO 2 , arteriolar partial pressure of oxygen; RDKA, recurrent DKA.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Management of Hyperglycemic Crises in Patients With Diabetes T E C H N I C A L R E V I E R e v i e w s / C o m m e n t a r i e s / P o s i t i o n S t a t e m e n t s 132DIABETES CARE, VOLUME 24, NUMBER 1, JANUARY 2001Technical Review noted in newly diagnosed obese type 2 diabetic patients (5,26,31). Therefore, the concept that the presence of DKA in type 2 diabetes is a rare occurrence is incorrect.The most common types of infections are pneumonia and urinary tract infection, accounting for 30-50% of cases (Table 4). Other acute medical illnesses as precipitating causes include alcohol abuse, trauma, pulmonary embolism, and myocardial infarction, which can occur both in type 1 and 2 diabetes (6). Various drugs that alter carbohydrate metabolism, such as corticosteroids, pentamidine, sympathomimetic agents, and ␣-and ␤-adrenergic blockers, and excessive use of diuretics in the elderly may also precipitate the development of DKA and HHS.The recent increased use of continuous subcutaneous insulin infusion pumps that use small amounts of short-acting insulin has been associated with an incidence of DKA that is significantly increased over the incidence seen with conventional methods of multiple daily insulin injections, in spite of the fact that most of the mechanical problems with insulin pumps have been resolved (6,(32)(33)(34). In the Diabetes Control and Complications Trial, the incidence of DKA in patients on insulin pumps was about twofold higher than that in the multipleinjection group over a comparable time period (35). This may be due to the exclusive use of short-acting insulin in the pump, which if interrupted leaves no reservoir of insulin for blood glucose control.Psychological factors and poor compliance, leading to omission of insulin therapy, are important precipitating factors for recurrent ketoacidosis. In young female patients with type 1 diabetes, psychological problems complicated by eating disorders may be contributing factors in up to 20% of cases of recurrent ketoacidosis (36,37). Factors that may lead to insulin omission in younger patients include fear of weight gain with good metabolic control, fear of hypoglycemia, rebellion against authority, and stress related to chronic disease (36). Noncompliance with insulin therapy has been found to be the leading precipitating cause for DKA in urban African-Americans and medically indigent patients (5,26). In addition, a recent study showed that diabetic patients without health insurance or with Medicaid alone had hospitali...

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“…Plasma concentrations of IL-6 and TNF-␣ were measured by Quantine High Sensitivity kits (R & D Systems, Minneapolis, MN). Plasma fatty acid and triglyceride concentrations were determined by using a microfluorimetric method (39).…”

Section: Proton Mrs Of Intramyocellular Triglyceride and Htg Contentmentioning

confidence: 99%

Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men

Petersen¹,

Dufour

Feng³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

353

332

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Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with increases in hepatic (HTG) and͞or intramyocellular lipid content, little is known about the prevalence of insulin resistance and potential differences in intracellular lipid distribution among healthy, young, lean individuals of different ethnic groups. To examine this question, 482 young, lean, healthy, sedentary, nonsmoking Eastern Asians (n ‫؍‬ 49), Asian-Indians (n ‫؍‬ 59), Blacks (n ‫؍‬ 48), Caucasians (n ‫؍‬ 292), and Hispanics (n ‫؍‬ 34) underwent an oral glucose tolerance test to assess whole-body insulin sensitivity by an insulin sensitivity index. In addition, intramyocellular lipid and HTG contents were measured by using proton magnetic resonance spectroscopy. The prevalence of insulin resistance, defined as the lower quartile of insulin sensitivity index, was Ϸ2-to 3-fold higher in the AsianIndians compared with all other ethnic groups, and this could entirely be attributed to a 3-to 4-fold increased prevalence of insulin resistance in Asian-Indian men. This increased prevalence of insulin resistance in the Asian-Indian men was associated with an Ϸ2-fold increase in HTG content and plasma IL-6 concentrations compared with Caucasian men. These data demonstrate important ethnic and gender differences in the pathogenesis of insulin resistance in Asian-Indian men and have important therapeutic implications for treatment of T2DM and for the development of steatosis-related liver disease in this ethnic group.gender and ethnic differences ͉ hepatic steatosis ͉ insulin resistance ͉ risk of type 2 diabetes

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Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.

Cited by 106 publications

References 37 publications

Relationship between insulin-mediated glucose disposal and lipid metabolism in man.

Relationship between insulin-mediated glucose disposal and lipid metabolism in man.

Management of Hyperglycemic Crises in Patients With Diabetes

Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men

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