scholarly journals GH replacement causing acute hyperglycaemia and ketonuria in a type 1 diabetic patient

2013 ◽  
Vol 2013 ◽  
Author(s):  
Dominic Cavlan ◽  
Shanti Vijayaraghavan ◽  
Susan Gelding ◽  
William Drake
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Type 1 Diabetes ◽  
Fatty Acid ◽  
Diabetic Patient ◽  
Acid Cycle ◽  
Gh Replacement ◽  
Glucose Fatty Acid Cycle ◽  
Gh Excess

Summary A state of insulin resistance is common to the clinical conditions of both chronic growth hormone (GH) deficiency and GH excess (acromegaly). GH has a physiological role in glucose metabolism in the acute settings of fast and exercise and is the only anabolic hormone secreted in the fasting state. We report the case of a patient in whom knowledge of this aspect of GH physiology was vital to her care. A woman with well-controlled type 1 diabetes mellitus who developed hypopituitarism following the birth of her first child required GH replacement therapy. Hours after the first dose, she developed a rapid metabolic deterioration and awoke with hyperglycaemia and ketonuria. She adjusted her insulin dose accordingly, but the pattern was repeated with each subsequent increase in her dose. Acute GH-induced lipolysis results in an abundance of free fatty acids (FFA); these directly inhibit glucose uptake into muscle, and this can lead to hyperglycaemia. This glucose–fatty acid cycle was first described by Randle et al. in 1963; it is a nutrient-mediated fine control that allows oxidative muscle to switch between glucose and fatty acids as fuel, depending on their availability. We describe the mechanism in detail. Learning points There is a complex interplay between GH and insulin resistance: chronically, both GH excess and deficiency lead to insulin resistance, but there is also an acute mechanism that is less well appreciated by clinicians. GH activates hormone-sensitive lipase to release FFA into the circulation; these may inhibit the uptake of glucose leading to hyperglycaemia and ketosis in the type 1 diabetic patient. The Randle cycle, or glucose–fatty acid cycle, outlines the mechanism for this acute relationship. Monitoring the adequacy of GH replacement in patients with type 1 diabetes is difficult, with IGF1 an unreliable marker.

Type 1 diabetes developed in a type 2 diabetic patient with severe insulin resistance

2005 ◽  
Vol 70 (3) ◽  
pp. 298-302 ◽  
Author(s):  
Tadashi Suehiro ◽  
Fumiaki Osaki ◽  
Yukio Ikeda ◽  
Kaoru Arii ◽  
Fumi Nakayama ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Diabetic Patient ◽  
Severe Insulin Resistance ◽  
Type 2 Diabetic

scholarly journals Fatty liver formation in fulminant type 1 diabetes

2016 ◽  
Vol 2016 ◽  
Author(s):  
Takashi Matsuo ◽  
Yoshihiko Ushiroda
Keyword(s):  
Fatty Acids ◽  
Type 1 Diabetes ◽  
Fatty Acid ◽  
Fatty Liver ◽  
Liver Dysfunction ◽  
Acid Metabolism ◽  
Fulminant Type 1 Diabetes ◽  
Level Of Consciousness ◽  
Fulminant Type

Summary A 32-year-old woman presented with 3days of epigastric pain and was admitted to our hospital (day 3 of disease). We diagnosed acute pancreatitis based on epigastric abdominal pain, hyperamylasemia, and an inflammatory reaction of withdrawn blood, pancreatic enlargement, and so on. Her condition improved with treatment; however, on day 8, she had decreased level of consciousness. Laboratory results led to a diagnosis of fulminant type 1 diabetes mellitus (FT1DM) with concomitant diabetic ketoacidosis. Insulin therapy improved her blood glucose levels as well as her symptoms. Fatty liver with liver dysfunction was observed on day 14, which improved by day 24. Blood levels of free fatty acids (FFAs) increased rapidly from 440μEq/L (normal range: 140–850μEq/L) on day 4 to 2097μEq/L on days 7–8 (onset of FT1DM) and subsequently decreased to 246μEq/L at the onset of fatty liver. The rapid decrease in insulin at the onset of FT1DM likely freed fatty acids derived from triglycerides in peripheral adipocytes into the bloodstream. Insulin therapy rapidly transferred FFAs from the periphery to the liver. In addition, insulin promotes the de novo synthesis of triglycerides in the liver, using newly acquired FFAs as substrates. At the same time, inhibitory effects of insulin on VLDL secretion outside of the liver promote the accumulation of triglycerides in the liver, leading to fatty liver. We describe the process by which liver dysfunction and severe fatty liver occurs after the onset of FT1DM, from the perspective of disturbed fatty acid metabolism. Learning points FT1DM is rare but should be considered in patients with pancreatitis and a decreased level of consciousness. Fatty liver should be considered in patients with FT1DM when liver dysfunction is observed. Insulin is involved in mechanisms that promote fatty liver formation. Pathophysiological changes in fatty acid metabolism may provide clues on lipid metabolism in the early phases of FT1DM.

scholarly journals FEATURES OF CHANGES IN FATTY ACIDS COMPOSITION OF TISSUES IN DIFFERENT MODELS OF EXPERIMENTAL TYPE 1 DIABETES

2018 ◽  
Vol 14 (3-4) ◽  
pp. 13-22
Author(s):  
Yu.S. Osadchuk ◽  
Yu.B. Chaykovskii ◽  
L.V. Natrus ◽  
T.S. Bryuzgina
Keyword(s):  
Fatty Acids ◽  
Type 1 Diabetes ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Liver Homogenate ◽  
Control Group ◽  
White Rats ◽  
Persistent Hyperglycemia

Relevance. Alloxan and streptozotocin are used for experimental modeling of hyperglycemia. Damaged β-cells with these compounds lead to the reduction of synthesis and secretion of the level of insulin in the blood, as a result of which animals develop hyperglycemia and diabetic syndrome, similar to insulin-dependent type 1 diabetes. One of the methodological approaches for assessing the degree and development of tissue damage of vital organs, including diabetes, is the study of their fatty acid composition. But for the planning of an experiment with type 1 diabetes, it is necessary to take into account the discrepancy between the data obtained on different models. Objective. The aim of the work is to study the changes in the fatty acid composition of cardiomyocyte and hepatocyte lipids in type 1 diabetes of the rats which are created on different models: alloxan (Allox) and streptozotocin (STZ). Material and methods. In the experiment, the model of type 1 diabetes was developed by the single-dose administration of streptozotocin (50 mg/kg) and alloxane monohydrate in a dose of 130 mg/kg to white rats. Their administration caused a persistent hyperglycemia (20-34 mmol/L) to the majority of experimental animals. Research of the contents of 9 most informative fatty acids (FA) in the composition of the myocardium and liver homogenate was carried out by gas-vapor chromatography in the experimental laboratory of Scientific research institute. The statistical significance of differences in the meanings of the groups of comparisons was estimated by the Student's t-criterion. Results. In the Allox model, we discovered a significant (p<0,05) 2-fold decrease in the proportion of palmitic FA to 9,5±0,5% relative to the control group 18,6±1,0% and stearic liquid crystal to 5,5±0,6% relative to the control 11,1±1,0% in the hepatocytes than in to STZ model. Additionally, we observed, a 12-fold increase in the content of meristic FA and pentadecane FA from 0,1±0,05% in the control to 1,2 ±0,1% in rats with the Allox model of diabetes. Among the unsaturated FA a significant increase (p <0,05) of 2,4 times the growth of oleinic FA from 14,8±1,5% to 34,2±1,6%, and a significant (p<0,05) in 1,5 times reduction of arachidone FA from 30,1±1,5% in control to 19,6±1,0% in rats with diabetes in the liver could be noted. A significant increase (p<0,05) of oleinic FA from 15,1±0,7 in the control to 33,1±1,5% and a decrease of 1,3 times the linoleic FA from 28,8±1,0% in control to 21,8±2,0% in the Allox model of rats with 1 type diabetes was showed in the myocardium. On the other hand, the STZ model rats increased the content of linoleic acid to 34,9±1,0%, which was a significant (p<0,05) difference with the control and Allox model. It is believed that the discrepancy in data is due to different pathogenetic mechanisms of action of drugs on tissues, which become targets of damage. Conclusions. The Allox model of type 1 diabetes shows the aggressive effects of high-level radicals and can be successfully used to study the mechanisms of oxidative stress, which necessarily occurs in conditions of hyperglycemia. The development of the STZ model of diabetes reflects the less awful effects of cell's damage, and such simulations should be used in the study of tissue and organ disorders that occur with prolonged and persistent hyperglycemia.

scholarly journals Effects of Growth Hormone and Free Fatty Acids on Insulin Sensitivity in Patients with Type 1 Diabetes

2009 ◽  
Vol 94 (9) ◽  
pp. 3297-3305 ◽  
Author(s):  
Burak Salgin ◽  
Maria L. Marcovecchio ◽  
Rachel M. Williams ◽  
Sarah J. Jackson ◽  
Leslie J. Bluck ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Growth Hormone ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

Context: Because GH stimulates lipolysis, an increase in circulating free fatty acid levels, as opposed to a direct effect of high GH levels, could underlie the development of insulin resistance in type 1 diabetes (T1D). Our aim was to explore the relative contributions of GH and free fatty acids to the development of insulin resistance in patients with T1D. Patients: Seven (four females, three males) nonobese patients with T1D aged 21–30 yr were studied on four occasions in random order. On each visit, overnight endogenous GH production was suppressed by octreotide. Three 1-h pulses of recombinant human GH (rhGH) or placebo were administered on two visits each. Acipimox, an antilipolytic drug, or a placebo were ingested every 4 h on two visits each. Stable glucose and glycerol isotopes were used to assess glucose and glycerol turnover. The overnight protocol was concluded by a two-step hyperinsulinemic euglycemic clamp on each visit. Main Outcome: rhGH administration led to increases in the insulin infusion rate required to maintain euglycemia overnight (P = 0.008), elevated basal endogenous glucose production (P = 0.007), decreased basal peripheral glucose uptake (P = 0.03), and reduced glucose uptake during step 1 of the clamp (P &lt; 0.0001). Coadministration of rhGH and acipimox reversed these effects and suppression of lipolysis in the absence of GH replacement led to further increases in insulin sensitivity. Results: GH pulses were associated with an increase in endogenous glucose production and decreased rates of peripheral glucose uptake, which was entirely reversed by acipimox. Therefore, GH-driven decreases in insulin sensitivity are mainly determined by the effect of GH on lipolysis. Growth hormone decreases insulin sensitivity through increases in free fatty acid levels.

scholarly journals Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes

Diabetes ◽  
2010 ◽  
Vol 60 (1) ◽  
pp. 306-314 ◽  
Author(s):  
Irene E. Schauer ◽  
Janet K. Snell-Bergeon ◽  
Bryan C. Bergman ◽  
David M. Maahs ◽  
Adam Kretowski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Fatty Acid ◽  
Coronary Artery ◽  
Coronary Artery Calcification ◽  
Acid Suppression

scholarly journals Palmitate inhibits liver glycolysis. Involvement of fructose 2,6-bisphosphate in the glucose/fatty acid cycle

1988 ◽  
Vol 251 (2) ◽  
pp. 541-545 ◽  
Author(s):  
L Hue ◽  
L Maisin ◽  
M H Rider
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Ketone Bodies ◽  
Acid Cycle ◽  
Glucose Fatty Acid Cycle ◽  
Inhibition Of Glycolysis ◽  
Beta Hydroxybutyrate ◽  
Fasted Rats

In hepatocytes from overnight-fasted rats incubated with glucose, palmitate decreased the production of lactate, the detritiation of [2-3H]- and [3-3H]-glucose, and the concentration of fructose 2,6-bisphosphate. Similarly, perfusion of hearts from fed rats with beta-hydroxybutyrate resulted in an inhibition of the detritiation of [3-3H]glucose and a fall in fructose 2,6-bisphosphate concentration. This fall could result from an increase in citrate (hepatocytes and heart) and sn-glycerol 3-bisphosphate concentration. It is suggested that a fall in fructose 2,6-bisphosphate concentration participates in the inhibition of glycolysis by fatty acids and ketone bodies.

scholarly journals FATTY ACID COMPOSITION OF SERUM LIPIDS IN PATIENTS WITH DECOMPENSATED TYPE 1 DIABETES MELLITUS DEPENDING ON THE DIABETIC KETOACIDOSIS SEVERITY

2019 ◽  
Vol 9 (3) ◽  
pp. 182-187
Author(s):  
N. V. Mukha ◽  
A. V. Govorin ◽  
E. B. Perevalova ◽  
D. N. Zajtsev
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acids ◽  
Type 1 Diabetes ◽  
Fatty Acid ◽  
Type 1 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Serum Lipids ◽  
Unsaturated Fatty Acids ◽  
Significant Difference

Summary. In diabetic ketoacidosis, significant metabolic disorders develop in all organs and tissues, including the myocardium. The main energy substrate in the myocardium are fatty acids.The objective was to study the fractional composition of serum lipids in patients with T1DM, complicated by diabetic ketoacidosis, depending on the severity ketoacidosis.Materials and methods. Determination of fatty acid spectrum of serum lipids was carried out in the following groups of patients: 68 patients with compensated type 1 diabetes mellitus (group 1), 54 patients with type 1 diabetes complicated by mild ketoacidosis (group 2); and 42 patients with diabetes mellitus complicated by moderate and severe ketoacidosis (3 group). Extraction of lipids from serum was performed according to the method developed by J. Folh et al. (1957), after which methylation of fatty acids was carried out according to the method proposed by K.M. Sinyak et al., with subsequent analysis using the Crystal-2000M gas chromatograph (Russia).Results. All patients with type 1 diabetes mellitus compared with a group of healthy individuals showed an increase in the total content of saturated fatty acids, a decrease in the total concentration of unsaturated fatty acids, as well as an increasing in the ratio of saturated / unsaturated fatty acids. At the same time, a significant difference between the studied groups was revealed. The most pronounced changes were found in the group of patients with type 1 diabetes mellitus complicated by moderate to severe ketoacidosis.Conclusions. These changes develop as part of a general systemic metabolic disorder in a given cohort of patients.

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