Endocrine Abstracts

Objective: Acromegaly is caused by a growth hormone (GH)-secreting pituitary tumor and its signs are linked to increasedGH-dependent hepatic insulin-like growth factor I (IGF-I) synthesis. A eucaloric very low-carbohydrate ketogenic diet (euVLCK; < 50 g/day) induces ketosis and reduces portal insulin concentrations, which down-regulate hepatic GH receptors and reduce IGF-I synthesis. Somatostatin receptor ligands (SRLs) reduce GH secretion by the pituitary tumor,resulting in IGF-I normalization in about 50% of patients. Remaining patients should switch to (or add) the expensive drug pegvisomant (PEGV). Our concept is that in acromegaly a euVLCK diet exerts insulin-induced IGF-I normalization without the unwanted increase in GH, as the GH-inhibiting SRL therapy is continued.

Method: We performed a proof-of-concept study (n = 11, six females) to determine whether a 2-week euVLCK diet (35 g carbohydrate, 155 g fat and 115 g protein/day) as adjuvant to first-generation SRLs reduces IGF-I concentrations in uncontrolled acromegaly patients.

Results: During the euVLCK diet, mean carbohydrate intake decreased from 194.4 [s.d. 143.1] gramsto 32.6 [14.7]. IGF-I concentrations decreasedsignificantly (median 0.83 [IQR 0.62 – 0.91] ULN vs 1.10 [1.02 –1.25], P = 0.014) and normalized in all but one patient, without the concomitant increase in GH (median 1.9 [IQR 0.4–3.7] µg/l vs 2.0 [0.7 – 3.6], P = 1.00). This patientstill showed substantial decrease in GH after the euVLCK diet and presented with the highest degree of insulin resistance. Overall, HbA1c decreased slightly(mean 38.6 [s.d. 4.4] mmol/mol vs 39.8 [5.2], P = 0.028). Insulin resistance, lipids and body composition did not change significantly. Although the diet was eucaloric, mean body weight decreased by about 1 kg. Of note, weight loss was not associated with changes in IGF-I concentrations (r_s = – 0.24, P = 0.47).Overall, the diet was well tolerated and all patients completed the study. Interestingly, SRL dose reduction was warranted in three out of six patients continuing a low-carbohydrate ketogenic diet (80 g/day; median 0.83 [IQR 0.75 – 1.01] ULN after median 3.0 months) as adjuvant to their initial SRL therapy.

Conclusion: This proof-of-concept study illustrates the ability of an adjuvant euVLCK diet to achieve control of IGF-I without affecting GH concentrations in acromegaly patients uncontrolled with first-generation SRLs. Our results could affect the clinical management of acromegaly as a euVLCK diet might deploy as an effective adjuvant treatment in some patientsbefore initiating PEGV treatment. Additional studies are needed to evaluate long-term safety and efficacy of and compliance with an euVLCK diet.