Clinical and biochemical studies on the significance and formation of hemoglobins AIc and AIa+b in diabetes mellitus

Dolhofer, Roswitha; Städele, A.; Wieland, O.

doi:10.1007/bf01479226

Cited by 34 publications

(27 citation statements)

References 30 publications

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“…There are conflicting reports on the correlation of Hb A I with the fasting concentrations of serum cholesterol and triglycerides [7,13,14,28]. In the present study, the Hb Ax values from Week 8 did correlate significantly with the mean serum triglyceride values for Week 3, 4 and 7 and with the serum cholesterol at Weeks 3 and 4 but these correlations were of a low magnitude.…”

Section: Discussioncontrasting

confidence: 73%

“…Reduced red cell survival in the diabetic is virtually excluded by the study of Peterson et al [27], for the observed reduction in life span was not adequate to explain the present observations. Dissociation of glycosylated haemoglobin in the stable ketoamine form also seems unlikely [13], but the possibility of a disproportionate increase in the reversible Schiff base moiety in the diabetic has not been excluded. A third theoretical possibility is a disproportionately accelerated synthesis of glycosylated haemoglobin at elevated blood glucose concentrations, but this also is purely conjectural.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the rate of decline of Hb Aic values following imposition of rigorous diabetic control in a group of five diabetics described by Koenig et al [12] appeared inconsistent with a reduction in rate of synthesis alone. Furthermore, high correlations have been reported between Hb Aic values and virtually simultaneous blood glucose concentrations [13,14]. Finally, short-term changes in blood glucose concen-O012-186X/79/0017/0213/$01.60 trations have been reported to influence Hb A~c values [15].…”

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confidence: 99%

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Temporal relationship of glycosylated haemoglobin concentrations to glucose control in diabetics

et al. 1979

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Summary. To examine the temporal relationship between Hb Aic values and various indices of blood glucose control, 38 diabetic and 28 nondiabetic youth counsellors employed at two summer camps for diabetic children took part in an eight-week study. Each week fasting determinations were made of Hb AI, Hb Al~ , serum cholesterol, triglyceride and growth hormone and plasma glucose. Total daily urine glucose excretion was measured approximately two times per week, capillary glucose values were measured fasting and at 11 a. m. and 3 p. m. on two days per week, and urine glucose was measured semiquantitatively four times per day. As Hb AI was correlated highly with Hb AI0 (r = 0.997), it was used as the primary index of glycosylated haemoglobin. The mean values of Hb AI, serum cholesterol and triglycerides and fasting plasma glucose were all significantly elevated in the diabetic group but only Hb AI values provided total separation of the two groups. Within the diabetic group the Week 8 Hb A I values showed a significant correlation with the Week 8 mean capillary glucose concentrations, the proportion of urine tests showing 2% and 0% glycosuria, and mean serum triglycerides. Correlations of Week 8 Hb A~ with the mean values of these glycaemic parameters for each week of the study demonstrated low order correlations with the glycaemie measures of Week 1, and a progressive increase in the degree of correlation reaching a plateau with the glycaernic measures of Week 4 to 8. Similar correlation analysis using the Hb Ai values from Week 4 confirmed these findings. Therefore, while Hb AI provides an index of the control of diabetes, it appears to be more acutely responsive to blood glucose alteration than generally recognized.

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Section: Discussioncontrasting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Temporal relationship of glycosylated haemoglobin concentrations to glucose control in diabetics

et al. 1979

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“…HbAIe is formed postfibosomally by attachment of glucose and mannose to the N-terminal valic, e of'the B-chains of HbA via a Schiff's base linkage [1][2][3][4][5], while the structure of I-IbAia+b ~as not yet been studied in comparable detail. The minor hemoglobins are elevated in diabetic patients [6--9], depending on the blood sugar level [9]. L-1 vitro, g~ucose stimulates ha a dose-dependent mar.her hemoglobin glycosylation in hemolysates from normal erythrocytes [5,9] and also in purified hemo#obha preparations [5,9].…”

mentioning

confidence: 99%

“…6 at 4°C with four changes in 36 h, and centrifuged at 40 900 X g for 39 rain at 4°C. Fracfionation and quantification of the minor hemoglobins was carried out as described [9].Separation of c~-and/~-chalns of hemoglobin was performed by chromatography on CM 23 ha 8 M urea according to [11,12]. The peak fractions were pooled and dialyzed at 4°C against tOO-fold voL 0.9% NaC1, pH 7.0, with four changes kt 36 h prior to about 50-fold concentration by eollodium bags SM ~sevier/ Nort&-Hogand ~'omed£cag -~esz …”

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confidence: 99%

In vitro glycosylation of hemoglobins by different sugars and sugar phosphates

Dolhofer¹,

Wieland²

1978

FEBS Letters

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HemogJobins Ah+ b (HbAh+b) and hemo~obin P.;:~ (HbAic) the so-called :tuner hem(,#obins are regular constituents of human exs, thrccytes. HbAIe is formed postfibosomally by attachment of glucose and mannose to the N-terminal valic, e of'the B-chains of HbA via a Schiff's base linkage [1][2][3][4][5], while the structure of I-IbAia+b ~as not yet been studied in comparable detail. The minor hemoglobins are elevated in diabetic patients [6--9], depending on the blood sugar level [9]. L-1 vitro, g~ucose stimulates ha a dose-dependent mar.her hemoglobin glycosylation in hemolysates from normal erythrocytes [5,9] and also in purified hemo#obha preparations [5,9]. In the present st-udy we show that ~ glycosylation is not specific for glucose out occurs also ~dth other sugars and sugar-phosphates. In every case incorporation took place mainly into the ~-ch~ns of the minor hemoglobins. M.~terials and methods Incorporation of sugars into hemoglobin chainsPrior to use the hemolysate was dialyzed at 4~C with three changes in 24 h against 100-fold vol. glucose-free Earle's solution [ 1 O] fortified with sotidMgSOa and NaHCO3 to yield final concentrations of 1.2 and 40 retool/liter, respectively. To 8 ml of hemolysate, placed in plastic tubes (2 X 10 cm) the labelled sugars were added to yield a final concentration of 22.2 mmolhiter and spec. radioact. 2.5 mCi/ mmol. The pH was adjusted to 7.5 by gassing for 5 mhl with carbogen (95:5[O2 :COz) before the plastic tubes were stoppered and incubated for 2 h at 37°C in a shaking water bath. The mixture was then immediately dialyzed against 1000-fold yd. developer no. 6 at 4°C with four changes in 36 h, and centrifuged at 40 900 X g for 39 rain at 4°C. Fracfionation and quantification of the minor hemoglobins was carried out as described [9].Separation of c~-and/~-chalns of hemoglobin was performed by chromatography on CM 23 ha 8 M urea according to [11,12]. The peak fractions were pooled and dialyzed at 4°C against tOO-fold voL 0.9% NaC1, pH 7.0, with four changes kt 36 h prior to about 50-fold concentration by eollodium bags SM ~sevier/ Nort&-Hogand ~'omed£cag -~esz

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Glycohemoglobins and Glucose Tolerance

Lev-Ran¹

1979

JAMA

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Glycohemoglobin (GHb) levels were assayed after chromatography on weakly acidic acrylic cationite columns in 167 patients undergoing glucose tolerance test (GTT) and in 105 known diabetics. In 95% of patients with normal GTT levels, the GHb level was in the range of 6.8% to 9.8%. The GHb level was normal in patients with latent diabetes. Glycohemoglobin levels were elevated in patients with poorly controlled diabetes. Even in patients with normal GTT results, GHb levels correlated positively with fasting plasma glucose and glucose tolerance values. In patients with abnormal GTT results or diabetes but not receiving insulin therapy, the correlation between GHb levels and fasting plasma glucose values was significant. The GHb level that distinguished between latent and overt diabetes correlated strongly with the values of fasting plasma glucose and glucose tolerance and reflected changes in the control of diabetes.

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Clinical and biochemical studies on the significance and formation of hemoglobins AIc and AIa+b in diabetes mellitus

Cited by 34 publications

References 30 publications

Temporal relationship of glycosylated haemoglobin concentrations to glucose control in diabetics

Temporal relationship of glycosylated haemoglobin concentrations to glucose control in diabetics

In vitro glycosylation of hemoglobins by different sugars and sugar phosphates

Glycohemoglobins and Glucose Tolerance

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