Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Pathophysiology/Complications

Influence of Hepatic Steatosis (Fatty Liver) on Severity and Composition of Dyslipidemia in Type 2 Diabetes

  1. Frederico G.S. Toledo, MD1,
  2. Allan D. Sniderman, MD2 and
  3. David E. Kelley, MD1
  1. 1Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
  2. 2Mike Rosenbloom Laboratory for Cardiovascular Research, Royal Victoria Hospital, Montreal, Quebec, Canada
  1. Address correspondence and reprint requests to Frederico G.S. Toledo, MD, 807N Montefiore Hospital, 3459 Fifth Ave., Pittsburgh, PA 15213. E-mail: toledofs{at}upmc.edu
Diabetes Care 2006 Aug; 29(8): 1845-1850. https://doi.org/10.2337/dc06-0455
PreviousNext
  • Article
  • Figures & Tables
  • Info & Metrics
  • PDF
Loading

Abstract

OBJECTIVE—The objective of this study was to examine the associations between the severity of hepatic steatosis and dyslipidemia in type 2 diabetes, including circulating apolipoprotein B100 (apoB) concentrations and lipoprotein particle size and numbers.

RESEARCH DESIGN AND METHODS—Computed tomography imaging was used to assess hepatic fat content and adipose tissue distribution in 67 men and women with type 2 diabetes, withdrawn from antidiabetic medications preceding the study. Fasting serum lipoprotein number and size was determined by nuclear magnetic resonance. Insulin sensitivity was measured with a glucose clamp and a [6,6-2H2]glucose isotope infusion.

RESULTS—Two-thirds of the cohort had fatty liver. Hepatic steatosis correlated with serum triglycerides (r = 0.40, P < 0.01) and lower HDL cholesterol (r = −0.31, P < 0.05). ApoB and LDL cholesterol did not, being virtually identical in those with or without steatosis. The association between serum triglycerides and hepatic steatosis was largely accounted for by greater triglyceride enrichment in VLDL particles, which were larger. Severe steatosis was also associated with 70% higher small, dense LDL concentrations. Visceral obesity did not fully explain these associations, and hepatic steatosis was better correlated with triglycerides than with hyperglycemia or hepatic insulin resistance (P > 0.05).

CONCLUSIONS—The presence of hepatic steatosis in type 2 diabetes does not appear to affect apoB levels, but potentially increases atherogenesis by increasing triglycerides, reducing HDL levels, and increasing small, dense LDL.

  • apoB, apolipoprotein B100
  • EGP, endogenous glucose production
  • FFA, free fatty acid
  • IDL, intermediate-density lipoprotein
  • L/S ratio, ratio of liver to spleen
  • NMR, nuclear magnetic resonance
  • VAT, visceral adipose tissue

Patients with type 2 diabetes typically have an atherogenic serum lipid profile that is characterized by hypertriglyceridemia, low HDL, small, dense LDL particles, and increased apolipoprotein B100 (apoB) concentrations (1–3). The central abnormality appears to be an increased rate of hepatic triglyceride synthesis and VLDL particle production, which results in secondary abnormalities of low HDL and increased LDL particle number and density. Insulin resistance is regarded as a major driving force for dyslipidemia, with one mechanism being an increase in free fatty acid (FFA) release, stimulating hepatic triglyceride output (2,4–7). Increased availability of FFAs within the liver also inhibits apoB degradation, stabilizing the formation of more VLDL (4).

In the current study, we were interested in the role of hepatic steatosis as an additional modifier and predictor of the severity of dyslipidemia in type 2 diabetes. Hepatic steatosis, also known as “fatty liver” or nonalcoholic fatty liver disease, is frequently observed in type 2 diabetes (8–11). In humans, it is recognized that hepatic steatosis is a predictor of insulin resistance (12–14), and it is also associated with hypertriglyceridemia in nondiabetic subjects (14). In type 2 diabetes, this association has also been reported (15). However, it remains unclear whether hepatic steatosis primarily induces an increased number of VLDL particles, as would be reflected in greater plasma apoB concentrations or primarily influences the triglyceride content of VLDL particles. The current study was undertaken to more precisely characterize the association between hepatic steatosis and the proatherogenic lipid profile in type 2 diabetes.

RESEARCH DESIGN AND METHODS

The protocol was approved by the University of Pittsburgh Institutional Review Board, and research volunteers gave written informed consent. Participants were recruited for two separate clinical investigations, as earlier described (15). Briefly, inclusion criteria included a BMI >27 kg/m2, a confirmed diagnosis of type 2 diabetes (<5 years of duration), and current treatment with a sulfonylurea, repaglinide, or metformin at submaximal doses (alone or in combination) or diet alone; good general health other than type 2 diabetes; no known cardiovascular disease; and a stable weight (<3 kg variation in the preceding 2 months). Exclusion criteria included elevations of serum transaminase or alkaline phosphatase, therapy with insulin, a thiazolidinedione, or fibrates, serum triglycerides >4.52 mmol/l (400 mg/dl), a history of hepatic disease, substance abuse, or daily consumption of more than one alcohol drink or the equivalent in beer and wine. Statin users were 13.4% of the cohort and uniformly distributed across tertiles of hepatic steatosis. Before metabolic and body composition measurements, participants were asked to withdraw from current diabetes medications for a 4-week baseline period. A dietitian met with participants to advise them to follow a weight maintenance nutritional plan with a balanced macronutrient composition. After this period, volunteers were admitted to the University of Pittsburgh General Clinical Research Center, where they received a standardized dinner (7 kcal/kg; 50% carbohydrate, 30% fat, and 20% protein) and fasted overnight before biochemical, metabolic, and body composition studies in the following morning.

Lipoprotein measurements

On the morning after admission, plasma and serum were obtained and stored at −70°C before biochemical analysis. Serum apoB concentration was determined by a variation of the Boehringer Mannheim turbidimetric procedure. HDL cholesterol was determined after selective precipitation by heparin-manganese chloride and removal by centrifugation of VLDL and LDL (16). Serum triglycerides (17) and total cholesterol (18) were determined as previously described. Plasma VLDL, LDL, and HDL particle number and size were determined by nuclear magnetic resonance (NMR) spectroscopy (NMR LipoProfile; LipoScience, Raleigh, NC). Particle subclasses were defined as follows: VLDL (>27–35 nm); intermediate-density lipoprotein (IDL) (23–27 nm); large LDL (21.2–23 nm); and small LDL (18–21.2 nm).

Body composition assessments

Fat and lean mass were determined by dual-energy X-ray absorptiometry (15,19). Computed tomography (CT) was used to measure hepatic steatosis and the cross-sectional area of adipose tissue in the abdomen and midthigh, as previously described in detail (15,19). Prior studies have shown a strong linear correlation between CT attenuation values in the liver and fatty infiltration measured by biopsy in a wide range of steatosis (20–23). The ratio of liver to spleen attenuation (L/S ratio) is a normalized index, with an L/S ratio <1 considered to represent fatty liver (20). Liver CT attenuations were determined by calculating the mean Hounsfield unit of three regions of interest of 120 mm2 in the liver (two in the right lobe and one in the left lobe) and that of spleen also, on the basis of the mean Hounsfield unit of three regions of interest of 75 mm2.

Insulin sensitivity.

Euglycemic clamps were used to measure insulin sensitivity, as previously described (24). Insulin was infused at 40 mU · m–2 · min–1 for 4 h. Plasma glucose was checked every 5 min and maintained at 100 mg/dl with a variable-rate dextrose infusion. To measure endogenous glucose production (EGP) (25), a primed (200 mg/m2), continuous (2 mg · min–1 · m–1) infusion of [6,6-2H2]glucose was given. [6,6-2H2]Glucose enrichment was determined by gas chromatography/mass spectrometry, as described previously (15). Plasma glucose was measured by the glucose-oxidase method (Yellow Springs Instruments, Yellow Springs, OH). FFAs were measured by an enzymatic method, and insulin was measured by a double-antibody radioimmunoassay (15).

Statistics

Data are presented as means ± SE, unless otherwise indicated. P values <0.05 were considered significant. ANOVA was used to test for differences across tertiles. Spearman analysis was used to determine correlations between variables.

RESULTS

The clinical characteristics of the research volunteers are shown in Table 1. The 67 participants were stratified according to tertiles of L/S ratio, which is inversely and linearly proportional to hepatic fat content (20,21). All subjects in the tertile with the lowest hepatic fat content had an L/S ratio >1.0, consistent with normal hepatic fat content (20), and thus this group is referred to as “normal” to denote the absence of fatty liver disorder. Subjects in the other tertiles had L/S ratios consistent with fatty liver and were labeled as “moderate” and “severe” to denote different degrees of hepatic steatosis.

Age and sex distributions were similar across the three groups. HbA1c (A1C), fasting plasma glucose, and FFAs were also similar among groups. Fasting insulin was higher in moderate and severe steatosis. Mean BMI was in the obese range and higher in the moderate group, but the percentage of weight accounted for by fat mass (percent body fat) was similar across groups. In terms of regional fat distribution, visceral adipose tissue (VAT) was significantly greater in the moderate and severe groups, but the amounts of abdominal subcutaneous adipose tissue and thigh subcutaneous adipose tissue were similar across groups. VAT was correlated with the L/S ratio (r = −0.47, P < 0.01).

Serum lipid profiles

Compared with the normal group, a pattern of increased serum triglycerides and reduced HDL cholesterol was seen in those with moderate and severe steatosis (Table 2). Although there were small differences in triglycerides and HDL cholesterol between the moderate and severe groups, these differences were not statistically significant.

ApoB concentrations were similar across groups, indicating that although hepatic steatosis is associated with greater serum triglyceride concentrations, this is not accompanied by an increase in plasma apoB-containing lipoproteins. LDL particles account for the majority of circulating apoB-containing lipoproteins, and, as expected, LDL and total cholesterol were similar across groups too. ApoB concentrations in this cohort of individuals with type 2 diabetes were significantly greater than the mean value observed in lean, nondiabetic individuals. Even in the normal group, the mean apoB concentration (0.94 ± 0.05 g/l) was significantly greater than the mean obtained from a separate group of 12 lean, insulin-sensitive, nondiabetic subjects with a mean age of 41.6 ± 1.9 years (0.73 ± 0.04 g/l, P < 0.05, not shown in the table).

Lipoprotein composition

To further examine the relationship between hepatic steatosis and lipoprotein composition and concentration, NMR spectroscopy of lipoprotein subfractions was performed in 19 randomly selected subjects from each group (Table 2). VLDL particles were larger in the moderate and severe steatosis groups compared with the normal group. Yet, the number of circulating VLDL particles was statistically indistinguishable across groups. This suggests that the association between hepatic steatosis and hypertriglyceridemia in type 2 diabetes is mostly accounted for by increased triglyceride content per VLDL particle. The increase in serum triglycerides with hepatic steatosis could not be attributed to chylomicrons, as these were nearly absent. We also observed that smaller LDL and HDL particles were associated with hepatic steatosis. However, the numbers of LDL and HDL particles did not differ. As noted in Table 2, severe steatosis was also associated with a 70% greater small, dense LDL particle concentration than in the normal group, and this was associated with a reciprocal lowering in large LDL. IDL subclass was not influenced by severity of hepatic steatosis.

Strength of correlation between serum lipids and hepatic steatosis

As shown in Fig. 1A, the L/S ratio, which is inversely proportional to hepatic fat, was significantly correlated with serum triglycerides (r = −0.40, P < 0.01). It also correlated with HDL cholesterol (r = 0.31, P < 0.05) but not with LDL cholesterol or apoB (P > 0.05). VAT also correlated with serum triglycerides (r = 0.51, P < 0.01) and weakly with apoB (r = 0.26, P < 0.05), although not with HDL cholesterol.

As shown in Fig. 1A, CIs in the association between hepatic steatosis and plasma triglyceride were greater with more severe steatosis. In support of this notion, the correlation between the L/S ratio and serum triglycerides within the tertile with minimal or no steatosis (normal), was substantially more robust (r = −0.69, P < 0.01) and is plotted in Fig. 1B. In this group, the association between serum triglycerides and VAT was no longer statistically significant (r = 0.37, P = 0.08).

Insulin resistance

We found that systemic insulin resistance was more severe in the moderate and severe groups of hepatic steatosis (Fig. 2). This was evident both by lower glucose disposal rates measured by the euglycemic clamp technique and by higher values for the fasting homeostasis model assessment of insulin resistance index. In contrast, fasting rates of EGP and insulin-suppressed EGP were equivalent across groups, indicating similar levels of hepatic insulin resistance.

CONCLUSIONS

Both hepatic steatosis and dyslipidemia commonly occur in obesity and type 2 diabetes. Fatty liver reflects hepatic oversupply of lipids, which we postulate marks a metabolic state conducive to hyperlipidemia. One of the main purposes of the current study was to examine whether hepatic steatosis is a predictor of a more severe dyslipidemia in type 2 diabetes. We found this to be the case. The presence of hepatic steatosis was associated with elevated serum triglycerides; small, dense LDL; and reduced HDL. A further observation concerns apoB. Insulin resistance is associated with increased apoB, and in general, there is higher apoB in type 2 diabetes (26,27). Levels of apoB were increased in the type 2 diabetic subjects of the current study but did not appear to be associated with the severity of hepatic steatosis or systemic insulin resistance. Our findings indicate that hepatic steatosis in type 2 diabetes is associated with increased triglyceride content per VLDL particle, rather than more increases in total VLDL particle numbers. Although we did not study apoB secretion kinetics, our findings are consistent with a model in which hepatic triglyceride content is not the only and perhaps not the principal determinant of hepatic VLDL-apoB secretion rate (28) but a more substantial determinant of triglyceride content in VLDL.

NMR spectroscopy was used to confirm these findings on lipoprotein composition. There was an increase in mean VLDL particle size but not number associated with hepatic steatosis, indicating the presence of triglyceride-enriched VLDL. Increased serum triglycerides were also strongly related to an increased proportion of small, dense LDL and decreased HDL. Although the total atherogenic particle number was not increased with hepatic steatosis, as noted by no increase in apoB, the risk of atherosclerosis might be raised by the greater numbers of small, dense LDL and perhaps even more significantly by reductions in HDL cholesterol and size that were noted.

There are three major methods to characterize lipoprotein subclasses: ultracentrifugation, gradient gel electrophoresis, and NMR. They differ not only in methodology but also in how what is measured is expressed. We chose the NMR methodology because it measures both particle numbers and size and has been successfully used in studies with insulin-resistant patients as well as in type 2 diabetes (29,30). It is important to note that in our study, the lipoprotein data from NMR were of a confirmatory nature, as the result can be anticipated from the measurements of triglycerides and apoB; a significant increase in triglycerides with no significant change in apoB should approximately equate to a higher triglyceride enrichment of VLDL.

Hepatic steatosis has not been traditionally regarded as a predictor of the severity of diabetic dyslipidemia, although the results of our study indicate that it should merit consideration. In fact, our study demonstrated that hepatic steatosis in type 2 diabetes is a better predictor of dyslipidemia severity than hyperglycemia or hepatic insulin resistance. Factors already regarded as influencing severity of diabetic dyslipidemia include hyperglycemia, increased plasma FFAs, and hyperinsulinemia; each of which is related to insulin resistance (2–5). Modest reductions in lipoprotein lipase activity may also contribute (31,32). It is of interest that in the current study, fasting hyperglycemia, A1C, and plasma FFA were quite similar across tertiles of hepatic steatosis, yet as earlier described, the severity of dyslipidemia differed. Although plasma insulin was higher in those with more steatosis, insulin was a much weaker correlate of serum triglycerides than hepatic steatosis. Together, these observations indicate the potential additional influence of hepatic steatosis as a predictor of the severity of diabetic dyslipidemia.

As in any association study, causality between variables is difficult to establish. However, the plausibility of causality should be considered. Because steatosis reflects increased lipid availability in hepatocytes, it is quite conceivable that hepatic steatosis reflects a state of increased hepatic FFA flux that stimulates VLDL triglyceride output. In agreement with this notion, liver-specific overexpression of lipoprotein lipase in mice, a manipulation intended to increase hepatic FFA uptake, causes a twofold increase in liver triglyceride content and fasting hypertriglyceridemia (33). The importance of VAT should also be considered (34). A limitation of our study is that the relative contributions of hepatic steatosis and VAT upon dyslipidemia cannot be easily separated because VAT and hepatic steatosis are tightly associated with each other. In fact, VAT and hepatic steatosis can be seen as components of the same pathophysiological process, one in which visceral adiposity promotes hepatic lipid overload. The portal circulation is uniquely exposed to visceral adipokine secretions and FFA flux from insulin-resistant visceral adipocytes (7,35). However, it is also important to recognize that the hepatic lipid content is not only a result of FFA delivery and lipogenesis but also depends on hepatic fatty acid disposal by mitochondrial oxidation or secretion in the form of VLDL triglyceride. Thus, hepatic steatosis may be more proximally connected to VLDL metabolism than VAT because it directly reflects the metabolic state of hepatic fat overload. This hypothesis could explain why serum triglycerides were observed to be better correlated with hepatic fat content than VAT, plasma insulin, or plasma FFAs. This hypothesis remains speculative though because kinetic studies of VLDL synthesis and clearance were not performed. Of interest, a subtle characteristic of the relationship between hepatic steatosis and hypertriglyceridemia was apparent in this cohort, with this relationship being stronger among subjects with minor grades of hepatic fat content and being weaker among subjects with moderate to severe steatosis. This observation points to a loss of proportionality between hepatic steatosis and serum triglycerides once more severe steatosis is present and may indicate that, perhaps, the incorporation of triglycerides into VLDL also has a finite capacity.

One additional limitation of our study is that the influence of estrogen was not stringently controlled for. Nonetheless, this influence was probably minor because men and women were uniformly represented among groups, and most women were postmenopausal and of similar age.

In summary, we have observed that hepatic steatosis is a determinant of the severity of the dyslipidemia in type 2 diabetes, an association that is more evident when mild-to-moderate levels of steatosis are present. The association between hepatic steatosis and dyslipidemia is not attributable to greater apoB levels but to changes in the composition of VLDL particles and associated reductions in HDL and increases in small, dense LDL.

Figure 1—
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1—

Correlation between serum triglycerides and hepatic steatosis (L/S ratio). A: Across the whole spectrum of steatosis (r = −0.40, P < 0.01). B: Correlation analyzed within the group with none or minimal steatosis, i.e., L/S ratios ≥1.0 (r = −0.69, P < 0.01).

Figure 2—
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2—

Measurements of insulin sensitivity in groups with normal, moderate, and severe steatosis. A: Insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp. LBM, lean body mass; Rd, systemic glucose disposal rate. B: Estimated insulin resistance under fasting conditions by the homeostasis model assessment of insulin resistance (HOMA-IR). C: Fasting EGP rates. D: Insulin-suppressed EGP rates during the euglycemic clamp. *P < 0.05, †P < 0.01 vs. normal group.

View this table:
  • View inline
  • View popup
Table 1—

Patient characteristics stratified by L/S ratio

View this table:
  • View inline
  • View popup
Table 2—

Serum lipoprotein profile, particle size, and numbers

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 5, 2006.
    • Received February 27, 2006.
  • DIABETES CARE

References

  1. ↵
    Haffner SM: Lipoprotein disorders associated with type 2 diabetes mellitus and insulin resistance. Am J Cardiol 90: 55i–61i, 2002
    OpenUrlPubMedWeb of Science
  2. ↵
    Goldberg IJ: Clinical review 124: diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab 86:965–971, 2001
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    Ginsberg HN: Review: efficacy and mechanisms of action of statins in the treatment of diabetic dyslipidemia. J Clin Endocrinol Metab 91:383–392, 2006
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    Adeli K, Taghibiglou C, Van Iderstine SC, Lewis GF: Mechanisms of hepatic very low-density lipoprotein overproduction in insulin resistance. Trends Cardiovasc Med 11:170–176, 2001
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    Julius U: Influence of plasma free fatty acids on lipoprotein synthesis and diabetic dyslipidemia. Exp Clin Endocrinol Diabetes 111:246–250, 2003
    OpenUrlCrossRefPubMedWeb of Science
  6. Taskinen MR: Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749, 2003
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    Lewis GF: Fatty acid regulation of very low density lipoprotein production. Curr Opin Lipidol 8:146–153, 1997
    OpenUrlCrossRefPubMedWeb of Science
  8. ↵
    Nadeau KJ, Klingensmith G, Zeitler P: Type 2 diabetes in children is frequently associated with elevated alanine aminotransferase. J Pediatr Gastroenterol Nutr 41:94–98, 2005
    OpenUrlCrossRefPubMedWeb of Science
  9. Clark JM, Diehl AM: Hepatic steatosis and type 2 diabetes mellitus. Curr Diab Rep 2:210–215, 2002
    OpenUrlPubMed
  10. Gupte P, Amarapurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, Patel N, Madan A, Amarapurkar A, Hafeezunnisa: Non-alcoholic steatohepatitis in type 2 diabetes mellitus. J Gastroenterol Hepatol 19:854–858, 2004
    OpenUrlCrossRefPubMedWeb of Science
  11. ↵
    Creutzfeldt W, Frerichs H, Sickinger K: Liver diseases and diabetes mellitus. Prog Liver Dis 3:371–407, 1970
    OpenUrlPubMed
  12. ↵
    Ryysy L, Hakkinen AM, Goto T, Vehkavaara S, Westerbacka J, Halavaara J, Yki-Jarvinen H: Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 49:749–758, 2000
    OpenUrlAbstract
  13. Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, Halavaara J, Yki-Jarvinen H: Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 87:3023–3028, 2002
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    Kim HJ, Kim HJ, Lee KE, Kim DJ, Kim SK, Ahn CW, Lim S-K, Kim KR, Lee HC, Huh KB, Cha BS: Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 164:2169–2175, 2004
    OpenUrlCrossRefPubMedWeb of Science
  15. ↵
    Kelley DE, McKolanis TM, Hegazi RA, Kuller LH, Kalhan SC: Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab 285:E906–E916, 2003
    OpenUrlAbstract/FREE Full Text
  16. ↵
    Warnick GR, Albers JJ: A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19:65–76, 1978
    OpenUrlAbstract
  17. ↵
    Bucolo G, David H: Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 19:476–482, 1973
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Allain CC, Poon LS, Chan CS, Richmond W, Fu PC: Enzymatic determination of total serum cholesterol. Clin Chem 20:470–475, 1974
    OpenUrlAbstract
  19. ↵
    Kelley DE, Kuller LH, McKolanis TM, Harper P, Mancino J, Kalhan S: Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes. Diabetes Care 27:33–40, 2004
    OpenUrlAbstract/FREE Full Text
  20. ↵
    Longo R, Ricci C, Masutti F, Vidimari R, Croce LS, Bercich L, Tiribelli C, Dalla Palma L: Fatty infiltration of the liver: quantification by 1H localized magnetic resonance spectroscopy and comparison with computed tomography. Invest Radiol 28:297–302, 1993
    OpenUrlCrossRefPubMedWeb of Science
  21. ↵
    Ricci C, Longo R, Gioulis E, Bosco M, Pollesello P, Masutti F, Croce LS, Paoletti S, de Bernard B, Tiribelli C, Dalla Palma L: Noninvasive in vivo quantitative assessment of fat content in human liver. J Hepatol 27:108–113, 1997
    OpenUrlCrossRefPubMedWeb of Science
  22. Piekarski J, Goldberg HI, Royal SA, Axel L, Moss AA: Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease. Radiology 137:727–729, 1980
    OpenUrlPubMedWeb of Science
  23. ↵
    Limanond P, Raman SS, Lassman C, Sayre J, Ghobrial RM, Busuttil RW, Saab S, Lu DS: Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings. Radiology 230:276–280, 2004
    OpenUrlCrossRefPubMed
  24. ↵
    DeFronzo RA, Tobin JD, Andres R: Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223, 1979
  25. ↵
    Wolfe R: Radioactive and Stable Isotope Tracers in Biomedicine. New York, Wiley Liss, 1992
  26. ↵
    Sniderman AD, Scantlebury T, Cianflone K: Hypertriglyceridemic hyperapoB: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus. Ann Intern Med 135:447–459, 2001
    OpenUrlCrossRefPubMedWeb of Science
  27. ↵
    Wagner AM, Perez A, Calvo F, Bonet R, Castellvi A, Ordonez J: Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients. Diabetes Care 22:812–817, 1999
    OpenUrlAbstract/FREE Full Text
  28. ↵
    Sniderman AD, Zhang XJ, Cianflone K: Governance of the concentration of plasma LDL: a reevaluation of the LDL receptor paradigm. Atherosclerosis 148:215–229, 2000
    OpenUrlCrossRefPubMed
  29. ↵
    Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, Pugh K, Jenkins AJ, Klein RL, Liao Y: Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 52:453–462, 2003
    OpenUrlAbstract/FREE Full Text
  30. ↵
    Goff DC Jr, D’Agostino RB Jr, Haffner SM, Otvos JD: Insulin resistance and adiposity influence lipoprotein size and subclass concentrations: results from the Insulin Resistance Atherosclerosis Study. Metabolism 54:264–270, 2005
    OpenUrlCrossRefPubMedWeb of Science
  31. ↵
    Nikkila EA, Huttunen JK, Ehnholm C: Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus: relationship to plasma triglyceride metabolism. Diabetes 26:11–21, 1977
    OpenUrlAbstract/FREE Full Text
  32. ↵
    Howard BV, Abbott WG, Beltz WF, Harper IT, Fields RM, Grundy SM, Taskinen MR: Integrated study of low density lipoprotein metabolism and very low density lipoprotein metabolism in non-insulin-dependent diabetes. Metabolism 36:870–877, 1987
    OpenUrlCrossRefPubMedWeb of Science
  33. ↵
    Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, Goldberg IJ, Breslow JL, Shulman GI: Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A 98:7522–7527, 2001
    OpenUrlAbstract/FREE Full Text
  34. ↵
    Despres JP: Health consequences of visceral obesity. Ann Med 33:534–541, 2001
    OpenUrlCrossRefPubMedWeb of Science
  35. ↵
    Frayn KN: Visceral fat and insulin resistance: causative or correlative? Br J Nutr 83 (Suppl. 1):S71–S77, 2000
    OpenUrl
PreviousNext
Back to top
Diabetes Care: 29 (8)

In this Issue

August 2006, 29(8)
  • Table of Contents
  • About the Cover
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Influence of Hepatic Steatosis (Fatty Liver) on Severity and Composition of Dyslipidemia in Type 2 Diabetes
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Influence of Hepatic Steatosis (Fatty Liver) on Severity and Composition of Dyslipidemia in Type 2 Diabetes
Frederico G.S. Toledo, Allan D. Sniderman, David E. Kelley
Diabetes Care Aug 2006, 29 (8) 1845-1850; DOI: 10.2337/dc06-0455

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Influence of Hepatic Steatosis (Fatty Liver) on Severity and Composition of Dyslipidemia in Type 2 Diabetes
Frederico G.S. Toledo, Allan D. Sniderman, David E. Kelley
Diabetes Care Aug 2006, 29 (8) 1845-1850; DOI: 10.2337/dc06-0455
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • RESEARCH DESIGN AND METHODS
    • RESULTS
    • CONCLUSIONS
    • Footnotes
    • References
  • Figures & Tables
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort
  • Gluconeogenesis, But Not Glycogenolysis, Contributes to the Increase in Endogenous Glucose Production by SGLT-2 Inhibition
  • Day-to-Day Variations in Fasting Plasma Glucose Do Not Influence Gastric Emptying in Subjects With Type 1 Diabetes
Show more Pathophysiology/Complications

Similar Articles

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.